RARE DISEASE
Thymic epithelial neoplasm
Thymic epithelial neoplasm
Thymic epithelial neoplasm
Synonyms: TEN, Thymic epithelial tumor
Synonyms: TEN, Thymic epithelial tumor
Synonyms: TEN, Thymic epithelial tumor
Drug discovery
4
drugs
With orphan designations
Overview
Thymic epithelial neoplasms (TENs) are rare malignancies originating from thymic epithelium, encompassing thymoma (most common), thymic carcinoma, and thymic neuroendocrine tumors. These tumors primarily arise in the anterior mediastinum and exhibit variable aggressiveness, with thymic carcinomas being the most aggressive. Clinical presentations range from asymptomatic incidental findings to paraneoplastic syndromes like myasthenia gravis (30-50% of thymomas). Diagnosis involves histopathology (WHO classification) and staging (Masaoka-Koga system), guiding multimodal therapy [1][4][7][12].
Population
Therapies
Resectable tumors: Complete thymectomy ± adjuvant radiotherapy (45–60 Gy), with VATS for early-stage lesions [3][5][20].
Unresectable/localized disease: Neoadjuvant platinum-based chemotherapy (CAP/carboplatin-paclitaxel) followed by surgery/radiotherapy [3][8][14].
Advanced/metastatic disease: Platinum-etoposide or anthracycline regimens; emerging therapies include sunitinib (VEGFR/PDGFR inhibitor) and PD-1 inhibitors (limited by autoimmune toxicity) [8][14][20].
Categories: rare neoplastic diseases
Research Papers
962 drug discovery papers about Thymic epithelial neoplasm, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
962 drug discovery papers about Thymic epithelial neoplasm, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-08-16 | Is phrenic nerve-sparing worthwhile for phrenic-involved thymic epithelial tumors? A retrospective cohort study.
To determine whether phrenic nerve (PN) sparing offers a worthwhile trade-off between functional preservation and oncologic safety compared with resection in PN-involved thymic epithelial tumors (TETs), and to establish an objective tool for postoperative respiratory risk stratification. In this retrospective cohort of patients with TETs with PN invasion, 122 propensity score-matched cases were analyzed from 2016 to 2024. PN preservation or resection was determined intraoperatively based on the extent of invasion. The diaphragmatic elevation (DE) ratio was calculated as [(preoperative diaphragm-apex distance - postoperative distance)/preoperative distance] × 100% according to X-rays, and cutoff values were defined by respiratory complication risk. Perioperative and oncologic outcomes were compared between the PN-sparing and PN resection groups. Overall perioperative morbidity and recovery outcomes were comparable between the PN-sparing and PN-resection groups; however, tumor progression was significantly more frequent on the PN-sparing group (39.3% vs 23.0%), resulting in worse progression-free survival (PFS) (P = .027), although overall survival (OS) remained comparable in the 2 groups. Multivariable analysis identified PN preservation as an independent predictor of progression (P = .049). Furthermore, our receiver operating characteristic-derived DE classification scheme (mild, ≤15%; moderate, 15-25%; severe, ≥25%) predicted severe postoperative respiratory complications (P < .001). PN resection improves PFS without increasing severe perioperative complications, although OS is comparable to that with PN-sparing.
2026-07-21 | Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026—A Narrative Review
Palliative systemic therapy for advanced thymic epithelial tumors (TET) is challenging due to scarce evidence and biological heterogeneity. Scientific discussion, as in this review, is limited to cross-trial comparisons of small, non-randomized studies. Platinum-based combination chemotherapy is the standard first-line treatment. Here, we challenge the addition of anthracyclines to platinum in thymoma. We critically appraise new combinations with antiangiogenic drugs and immune checkpoint inhibitors (ICI) in thymic carcinoma and their implications for therapy sequences. We review the data on classic genomics-based targeted therapy that does not benefit most patients and explore established and upcoming biomarkers including KIT and HER2. Finally, we discuss investigational therapies like anti-TROP2 antibody-drug conjugates and proteasome inhibitors, as well as topics and design of future research.
2026-07-11 | Identification of CCL4-positive macrophages and their associated immune microenvironment in thymic epithelial tumors
Thymic epithelial tumors (TETs) are one of the primary tumor types in the mediastinum, originating from thymic epithelial cells. Recent studies have highlighted the close association between specific macrophage subpopulations and the tumor immunosuppressive microenvironment. However, the characteristics and immunological functions of macrophages within TETs are still poorly understood. Single-cell transcriptome sequencing and the TCGA-THYM data were collected for integrated analysis of macrophage characteristics. The target cells were verified using multiplex immunofluorescence (mIF) staining. Functional validation was performed using Western blot and Transwell migration assays. Drug sensitivity was evaluated by predicting the half-maximal inhibitory concentration through oncoPredict. A group of CCL4 + macrophage subpopulations was clustered from the TETs myeloid single-cell subpopulation. By cell communication analysis, CCL4 + macrophages were positively correlated with exhausted T cells and regulatory T cells (Tregs). mIF staining confirmed a significant positive association between CCL4 + CD163 + cells and FOXP3 + CD4 + cells in terms of their proportions (r = 0.679, p < 0.001). Furthermore, in vitro experiments demonstrated that macrophages promoted Treg migration, which was significantly reduced by CCL4 blockade ( p < 0.05). Additionally, there are significant differences in drug sensitivity predictions and survival between TET patients with high and low CCL4 expression. These findings suggest that CCL4 + macrophages are specifically present in TETs and are related to the immune microenvironment of Treg infiltration.The expression of CCL4 in other immune cell subpopulations and cohorts still needs further verification to clarify its unique role in TET macrophages.
2026-07-10 | Pathobiology of thymic epithelial tumours and the treatment strategy based on immuno-oncological characteristics: a narrative review.
Thymic epithelial tumours (TETs), including thymomas and thymic carcinomas, are relatively rare anterior mediastinal malignancies. Thymomas are well known to be associated with various autoimmune diseases, such as myasthenia gravis (MG), pure red cell aplasia, and hypogammaglobulinemia. The mainstay of treatment for all TETs is complete surgical resection, although recent advances in irradiation and anti-tumour drug therapies are increasingly indicated for advanced or recurrent disease. The pathobiology of TETs was reviewed to consider optimal treatment strategies based on their immuno-oncological characteristics. A comprehensive literature search was conducted using PubMed, focusing on the biology and treatment of TETs, along with integration of our original research data. Pathobiology is different between thymoma and thymic carcinoma. Incomplete T cell development is observed in thymoma, which may affect patient autoimmunity. Type AB, B1, and B2 thymomas harbour abundant immature T cells, which cannot act as effector T cells in treatment using immune checkpoint inhibitors (ICIs). Neoplastic thymic epithelial cells (TECs) express programmed cell death-ligand 1 (PD-L1) at varying levels, and frequent genetic aberrations are observed according to the World Health Organization (WHO) classification. Germinal centre formation in the surrounding thymus may have a clinical role in thymoma-associated MG. Regarding treatment strategies, radical minimally invasive thymectomy using robotic technology is now available for MG. Effective molecular-targeted and ICI therapies have recently been introduced, and further novel targeted therapies are currently under development. WHO histological subtypes and inflammatory biomarkers are practically useful for determining the treatment strategy. A fundamental understanding of pathobiology and immuno-oncology is crucial for the appropriate management of TETs.
2026-07-10 | Systemic therapy for advanced thymic epithelial tumors: a narrative review of current evidence and perspectives.
Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare tumors. Although systemic therapy is commonly used for unresectable advanced or recurrent TETs, establishing robust evidence remains challenging. This narrative review summarizes current evidence and incorporates the latest clinical trial data, reporting outcomes separately for thymoma and thymic carcinoma whenever possible. We also highlight practical considerations relevant to clinical practice, including dosing strategies and toxicity management. We searched PubMed and Google Scholar for prospective and retrospective original studies, meta-analyses, review articles, and case studies published up to November 2025 using terms including "thymoma", "thymic carcinoma", "thymic cancer", "thymic tumors", "thymic epithelial tumors", "chemotherapy", "systemic treatment", "immunotherapy", and "targeted therapy". Ongoing trials were identified via ClinicalTrials.gov and the Japan Registry of Clinical Trials. Retrospective studies enrolling fewer than 15 participants were excluded. Systemic therapy for advanced TETs continues to include cytotoxic chemotherapy as a major component. In selected settings, particularly in thymic carcinoma, targeted therapy and immune checkpoint inhibitors (ICIs) represent additional active options. Emerging trials suggest that combination strategies may enhance efficacy. Novel drugs, including bispecific antibodies and antibody-drug conjugates, are being evaluated in ongoing phase II trials. Despite the rarity of TETs, systemic treatment options have gradually expanded through the accumulation of evidence from small phase II studies. Future advances will require collaborative prospective trials to validate predictive biomarkers and support biomarker-enriched trial designs.
proteins
2025-05-28 | Leveraging AI predictive models to develop thymic tumor–specific peptides mimicking COL17A1 alterations.
e20138 Background: We recently identified COL17A1 protein as a novel target in thymic epithelial tumors (TETs). Here, we designed tumor-specific peptides to mimic mutation regions in COL17A1. These peptides are intended as tools to generate antibodies targeting mutation-specific epitopes on COL17A1. Methods: In TCGA dataset, E391Kfs12, V809A, and P1409L alterations were frequently observed in the COL17A1 gene across various tumors, including TETs. The COL17A1 sequence was retrieved from UniProt, and mutations were introduced individually and in combination into the sequence. BLAST alignment analysis enabled direct comparison between the wild type and altered amino acid sequences. Next, we developed peptides of 8-10 Amino Acid (AA) around each mutation. We assessed the biophysical properties, immunogenicity (NetMHCpan), B-cell epitope prediction (Kolaskar), surface accessibility (Emini), solubility (NetSolP), thermal stability (TempStatPro) and enzyme function (TFPC). AlphaFold-3 analyzed predicted Template Modeling (pTM) and Local Distance Difference Test (pLDDT) scores for global folding and local stability, respectively. Results: Among the mutations, E391Kfs12 was located intracellularly, while V809A, and P1409L were extracellular. Using MutaGene, P1409L & E391Kfs12 were functionally deleterious. Next, a total of 144 peptides were designed to mimic mutations, including single and combined alteration. COL17A1 peptides had stronger binding affinity to MHC class I compared to class II. HLA-A24:02 & HLA-A26:01 (Score-BA 0.01) the strongest peptide-HLA-I affinity. The T-cell Immunogenicity predictions indicated the highest score for peptides near P1409L (Max 0.1). Emini surface accessibility showed the highest cell surface expression for E391Kfs12 (2.03) and P1409L (1.89). Epitope Conservancy Analysis evaluated matches with target and related sequences, with P1409L achieving the best score of 80% (range 55%–90%). Next, we divided peptides into 6 groups based on mutation sites. We assessed pLDDT (0–100), where high scores indicate strong local structural confidence. Single peptides had pLDDT >90, while most grouped peptides had scores <70. Peptides mimicking E391Kfs12 showed highest solubility (mean: 0.64, 0.60–0.78) and strong thermal stability at 45°C. P1409L peptides exhibited high enzymatic activity (mean: 0.48) but lower thermal stability (>70°C). V809A peptides demonstrated intermediate solubility (mean: 0.54) and stability, requiring optimization. Conclusions: AI predictive models enabled the design of thymic-tumor-specific peptides mimicking COL17A1 alterations. E391Kfs12 peptides with superior solubility and stability, and P1409L peptides, with strong immunogenicity, are promising candidates for antibody epitope generation. These findings provide a foundation for developing mutation-specific antibodies targeting thymic epithelial tumors.
2023-10-31 | MA08.05 Combining SBRT with GM-CSF and Peg-IFNα to Induce Abscopal Effects in Previously Treated Patients with Stage IV Thymic Tumors
After the failure of multi-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis.
2022-07-19 | A Proposed Link Between Acute Thymic Involution and Late Adverse Effects of Chemotherapy.
Epidemiologic data suggest that cancer survivors tend to develop a protuberant number of adverse late effects, including second primary malignancies (SPM), as a result of cytotoxic chemotherapy. Besides the genotoxic potential of these drugs that directly inflict mutational burden on genomic DNA, the precise mechanisms contributing to SPM development are poorly understood. Cancer is nowadays perceived as a complex process that goes beyond the concept of genetic disease and includes tumor cell interactions with complex stromal and immune cell microenvironments. The cancer immunoediting theory offers an explanation for the development of nascent neoplastic cells. Briefly, the theory suggests that newly emerging tumor cells are mostly eliminated by an effective tissue immunosurveillance, but certain tumor variants may occasionally escape innate and adaptive mechanisms of immunological destruction, entering an equilibrium phase, where immunologic tumor cell death "equals" new tumor cell birth. Subsequent microenvironmental pressures and accumulation of helpful mutations in certain variants may lead to escape from the equilibrium phase, and eventually cause an overt neoplasm. Cancer immunoediting functions as a dedicated sentinel under the auspice of a highly competent immune system. This perspective offers the fresh insight that chemotherapy-induced thymic involution, which is characterized by the extensive obliteration of the sensitive thymic epithelial cell (TEC) compartment, can cause long-term defects in thymopoiesis and in establishment of diverse T cell receptor repertoires and peripheral T cell pools of cancer survivors. Such delayed recovery of T cell adaptive immunity may result in prolonged hijacking of the cancer immunoediting mechanisms, and lead to development of persistent and mortal infections, inflammatory disorders, organ-specific autoimmunity lesions, and SPMs. Acknowledging that chemotherapy-induced thymic involution is a potential risk factor for the emergence of SPM demarcates new avenues for the rationalized development of pharmacologic interventions to promote thymic regeneration in patients receiving cytoreductive chemotherapies.
2019-11-22 | Follistatin impacts Tumor Angiogenesis and Outcome in Thymic Epithelial Tumors
Abstract Tumor angiogenesis is a key factor in the progression of thymic epithelial tumors (TETs). Activin A, a member of the TGFβ family, and its antagonist Follistatin are involved in several human malignancies and angiogenesis. We investigated Activin A and Follistatin in serum and tumor tissue of patients with TETs in relation to microvessel density (MVD), WHO histology classification, tumor stage and outcome. Membranous Activin A expression was detected in all tumor tissues of TETs, while Follistatin staining was found in tumor nuclei and cytoplasm. Patients with TETs presented with significantly higher Activin A and Follistatin serum concentrations compared to healthy volunteers, respectively. Follistatin serum concentrations correlated significantly with tumor stage and decreased to physiologic values after complete tumor resection. Follistatin serum concentrations correlated further with MVD and were associated with significantly worse freedom from recurrence (FFR). Low numbers of immature tumor vessels represented even an independent worse prognostic factor for FFR at multivariable analysis. To conclude, the Activin A - Follistatin axis is involved in the pathogenesis of TETs. Further study of Follistatin and Activin A in TETs is warranted as the molecules may serve as targets to inhibit tumor angiogenesis and tumor progression.
2019-04-01 | WT1 as an immunotherapy target for thymic epithelial tumors: a novel method to activate anti-tumor immunity
Thymic epithelial tumors (TETs) are family of rare cancers that exhibit diverse histology and variable clinical behavior (1). A significant fraction of patients, especially those with thymic carcinoma, have locally-advanced or metastatic disease at diagnosis that is often unresectable (1). Chemotherapy is associated with objective response rates (ORR) of 50–90% in the front-line setting, but limited benefit is observed in patients with recurrent disease (1,2). With few exceptions, biological agents have not demonstrated clinically meaningful activity in relapsed or refractory TETs (3). A low tumor mutation burden and paucity of actionable biological targets creates challenges for the development of targeted therapies for TETs (4,5). Hence, there is a pressing need to develop new treatments, especially for patients with advanced thymic carcinomas.
small molecules
2026-07-09 | PRRC2A-mediated m6A modification on NCOA4 promotes thymic epithelial tumor progression through PKM2-induced glycolysis.
Thymic epithelial tumors (TETs) are heterogeneous neoplasms. While most early-stage cases are curable after resection, advanced or aggressive subtypes have limited treatment options and poor outcomes. The molecular mechanisms underlying their metabolic reprogramming remain poorly understood. Proline-rich Coiled-coil 2a (PRRC2A), a N6-methyladenosine (m6A) reader protein, is significantly upregulated in TET tissues and is associated with poor clinical outcomes. Multi-omics analyses and molecular experiments revealed that PRRC2A binds to m6A-modified sites within the NCOA4 mRNA, thereby stabilizing NCOA4 transcripts and enhancing its protein expression. Elevated NCOA4 interacts with PKM2, a rate-limiting glycolytic enzyme, resulting in increased glycolysis and promoting TETs progression. In vivo experiments showed that inhibition of PRRC2A suppressed tumor growth and metastasis in TETs, while combined treatment with the PKM2 inhibitor C599 and PRRC2A knockdown produced enhanced antitumor effects. These findings provide novel insights into the glycolytic metabolic regulation of TETs and suggest that the PRRC2A-NCOA4-PKM2 axis represents a promising therapeutic target.
2026-07-01 | 153P Efficacy and safety of lenvatinib in patients with thymic epithelial tumors: A retrospective, multicenter study
Thymic epithelial tumors (TETs) are rare malignancies with limited options after standard platinum-based chemotherapy. While the REMORA trial confirmed the efficacy of lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), in thymic carcinoma (TC) patients with progressive disease, data for broader TET subtypes remain scarce. This study evaluated lenvatinib's efficacy and safety in patients with TETs, including TC and advanced malignant thymoma.
2026-06-26 | Redefining therapeutic horizons in thymic epithelial tumors: precision, combinations, and emerging biology
Thymic epithelial tumors (TETs) are rare and diverse cancers with distinctive immune features, limited prospective evidence, and few systemic options. Their association with autoimmunity, especially thymomas, complicates treatment decisions. This review examines molecular profiling and predictive biomarkers in TET and explores new treatment strategies. We highlight priorities for future trials, global registries, and real-world data to expand access to expert, multidisciplinary care, charting a path toward precision-guided, combination-based treatments.
2026-06-26 | Platinum-Based Chemotherapy with Novel Systemic Therapies in Patients with Unserectable or Metastatic Thymic Epithelial Tumors: A Systematic Review and Single-Arm Meta-Analysis
All articles of this category (opens in new window) Address for correspondence Gabriela Barbosa Silva (gabrielabarbosa20161@hotmail.com) Introduction: Thymic epithelial tumors (TETs) are rare malignancies with poor prognosis and limited evidence guiding systemic treatment in advanced stages. Following progression on platinum-based chemotherapy, no standard second-line treatment has been established. In recent years, immune checkpoint inhibitors (ICIs) and anti-angiogenic agents have been investigated in combination with chemotherapy to enhance therapeutic efficacy. However, the benefit of these combinations remains unclear. Objective: To evaluate the efficacy of platinum-based chemotherapy combined with novel systemic therapies as a first-line treatment for advanced TETs . Methods: A systematic search of PubMed, Embase, and Cochrane databases was conducted for studies involving histologically confirmed thymoma or thymic carcinoma with unresectable, locally advanced, recurrent, or metastatic disease, treated in the first-line setting with platinum-based doublets plus ICIs or anti-angiogenic agents. Studies on early-stage, resectable tumors, monotherapy regimens, or prior systemic therapy were excluded. Meta-analyses were performed using a random-effects model. Heterogeneity was assessed with the I² statistic and Cochran’s Q test. Sensitivity and subgroup analyses were conducted using meta-analyses of proportions. Results: Of 762 records screened, five phase II trials and four cohort studies met the inclusion criteria, comprising 206 patients (93.7% thymic carcinoma, 6.3% thymoma). Pooled analysis showed a median duration of response of 12.32 months (95% CI: 5.43–27.93), a median progression-free survival of 13.69 months (95% CI: 8.45–22.19), and an objective response rate (ORR) of 58.9% (95% CI: 45.7–71.0). ORR was higher with anti-angiogenic agents 68.5% (95% CI: 52.5–81.0) than with ICIs 52.0%, (95% CI: 35.9–67.6; p = 0.1472). A statistically significant difference in partial response rates was observed between anti-angiogenic agents 68.5% and ICIs 46.9% (p = 0.0898). Conclusion: Despite the lack of randomized evidence, platinum-based chemotherapy combined with anti-angiogenic agents may represent a promising first-line strategy for patients with advanced TETs, particularly those with thymic carcinoma. Prospective evaluation is warranted to validate these results. Publication History Article published online: 26 June 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil Bibliographical Record Gabriela Barbosa Silva, Lorrany Rodrigues Costa, Bianca Gonzaga Freitas, Letícia Peixoto Gomes, Filipe Luís Vasconcelos Visani. Platinum-Based Chemotherapy with Novel Systemic Therapies in Patients with Unserectable or Metastatic Thymic Epithelial Tumors: A Systematic Review and Single-Arm Meta-Analysis. Brazilian Journal of Oncology 2026; 22. DOI: 10.1055/s-0046-1825474
2026-05-28 | Surufatinib for advanced or metastatic chemotherapy-refractory thymic epithelial tumor: A single-arm, single-center, phase II study.
8119 Background: Thymic epithelial tumors (TETs), though relatively rare, represent the most common anterior mediastinal malignancy in adults. Platinum-based regimens are the standard first-line therapy; however, treatment options for subsequent lines remain poorly defined. Surufatinib, an oral tyrosine kinase inhibitor targeting VEGFR1/2/3, FGFR1, and CSF-1R, exerts both anti-angiogenic and immune-modulating effects. This study aimed to evaluate the efficacy and safety of surufatinib in patients (pts) with type B2/B3 thymoma (TM) or thymic carcinoma (TC), providing a potential new therapeutic strategy for TETs following anthracycline/taxane-based therapy. Here, we report the initial results. Methods: This was a single-arm, prospective phase II study. Eligible pts had histologically or cytologically confirmed, unresectable or radiotherapy-ineligible, advanced recurrent or metastatic B2/B3 TM or TC, with progression following at least one prior platinum-based chemotherapy regimen. Pts were aged >18 years and had at least one measurable lesion per RECIST 1.1 criteria. Treatment consisted of surufatinib 300 mg orally once daily in a 4-week cycle. Tumor assessments were conducted every 8 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Results: As of December 25, 2025, 20 pts were enrolled and evaluated. The median age was 55.5 years (range: 35–69), with 55% being male. Pathological subtypes included B2 TM (30%), B3 TM (15%), and thymic squamous cell carcinoma (TSCC, 55%). Eighteen pts (90%) presented with >5 metastatic sites. Ten pts (50%) achieved a partial response, and ten pts (50%) achieved stable disease. The ORR was 50%, and the DCR was 100%. With a median follow-up of 9.50 months, the median PFS was 11.9 months, and the 9-month PFS rate was 73.5%. Median OS was not reached, with an 18-month OS rate of 91.7%. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (70%), diarrhea (40%), elevated bilirubin (40%), and elevated transaminases (25%). Grade 3 TRAEs included hypertension (15%), diarrhea (5%), and elevated transaminases (5%). No treatment-related deaths were reported. Conclusions: Surufatinib monotherapy demonstrated promising antitumor activity and a manageable safety profile in patients with previously treated, advanced recurrent or metastatic TETs, supporting further investigation in this population. Clinical trial information: ChiCTR2600116776.
cell therapies
2026-02-26 | When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity
Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good's syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.
2026-01-07 | Oncological Outcomes of Complete Versus Limited Thymectomy in Early Stage Thymic Epithelial Tumors: A Systematic Review and Individual Patient Data Meta-Analysis
Objectives: To clarify the role of limited versus complete thymectomy in stage I thymic epithelial tumors (TETs) using standardized survival measures and predefined oncological outcomes. Methods: An individual patient data (IPD) meta-analysis of studies investigating complete versus limited thymectomy for stage I TETs was conducted. IPD was extracted from published Kaplan-Meier curves using the IPDfromKM method.Primary end point of the study was freedom from recurrence (FFR) in complete versus limited thymectomy. Secondary end points were time to progression (TTP), overall survival, recurrence rate in the overall population and stratified per Masaoka-Koga stage, and survival measures according to resection extension (thymomectomy alone versus hemi-thymectomy versus subtotal thymectomy).Hazard ratios and relative 95% confidence intervals (95% CIs) were estimated with Cox regression analyses. Odds ratio (OR) with 95% CI was used to derive categorical variables. Results: = 0.02).Finally, in those receiving limited thymectomy, thymomectomy alone had the worst FFR. Conclusion: No evidence favored limited than complete thymectomy in early stage TET treatment according to standardized survival measures. However, in Masaoka-Koga stage II disease, complete thymectomy demonstrated lower recurrence rate. Finally, among patients receiving limited thymectomy, thymomectomy alone leads to worse prognosis.
2025-10-09 | Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis
Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear. Materials and Methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors. Results: Among patients with clinical-stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (p = 0.0027) and higher recurrence risk (p < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group. Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence.
2025-04-10 | <i>De novo</i> Thymus Reconstitution: The Rising of Cell-based Strategies
The thymus plays a crucial role in the generation of functional T cells, which are essential in adaptive immune responses. However, the involution, dysfunction, and even absence of the thymus induced by various factors such as aging, heredity, tumor, infection, and surgical removal, greatly impair or completely deprive the normal functions of the thymus and has been threatening the health of countless patients. Thus, reconstituting the thymus in these patients is remarkably necessary and urgent, in which thymus transplantation is viable, but the rare donors and related complications dramatically limit its clinical application. Other exogenous regeneration therapies, like sex steroid inhibition and cytokines treatments, usually have nonspecific, limited, and transient outcomes. By comparison, <i>de novo</i> cell-based strategies to reconstitute the thymus may be more feasible, which can generate fully functional thymuses usually using autologous cells without the dependence on limited thymus donors, thus avoiding transplant donor shortage as well as related complications, and overcome the defects of exogenous regeneration therapies. In this review, we summarized the progression in this field, including the generation of functional thymic epithelial cells (TECs), the clonogenic culture of TECs, stem cell treatment, and the construction of thymic organoids, to provide a global perspective for cell-based <i>de novo</i> thymus reconstitution.
2025-01-23 | Transplantation of the MSLN‐deficient Thymus Generates MSLN Epitope Reactive T Cells to Attenuate Tumor Progression
ABSTRACT The development of mesothelin (MSLN) epitope reactive T cells is observed in mice that are immunized with the MSLN vaccine. Engineered T cells expressing MSLN‐reactive high‐affinity TCR exhibit extraordinary therapeutic effects for invasive pancreatic ductal adenocarcinoma in a mouse model. However, the generation of MSLN‐reactive T cells through the introduction of MSLN ‐deficient thymus and the transplantation of the latter as a cure for cancer treatment have not been tested to date. In the present study, the expression of MSLN was mainly identified in medullary thymic epithelial cells (mTECs) but not in hematopoietic cells, cortical thymic epithelial cells (cTECs), endothelial cells, or fibroblast cells in the thymus. The increasement of activated T cells was observed in MSLN‐expressing tumors from MSLN ‐deficient mice, indicating that MSLN‐reactive T cells had developed. Finally, in an AOM‐DSS‐induced mouse model of colorectal cancer (CRC), transplantation of MSLN ‐deficient thymus repressed the progression of CRC, accompanied by an increased number of IFNγ‐expressing T lymphocytes in the tumors. The data from this study demonstrated that ectopic transplantation of MSLN ‐deficient thymus induced MSLN‐specific antitumor responses to MSLN‐expressing tumors, and thus attenuated tumor progression.
other
2023-04-04 | Genomic characterization of thymic epithelial tumors reveals critical genes underlying tumorigenesis and poor prognosis.
Thymic epithelial tumors (TETs) are rare mediastinal tumors whose tumorigenesis mechanism is poorly understood. Characterization of molecular alterations in TETs may contribute to a better understanding of tumorigenesis and prognosis. Hybrid capture-based next-generation sequencing was performed on tumor tissues from 47 TETs (39 thymomas and 8 thymic carcinomas) to detect mutations in 315 tumor-associated genes. In total, 178 nonsynonymous mutations were identified, with a median of 3.79 per tumor in 47 TETs. Higher tumor mutation burden (TMB) level was more common in older TET patients, and significantly associated with the more advanced pathological type, especially in thymic carcinomas (TC) patients. The gene mutation profiles of B1-3, A/AB, and TC patients varied greatly. In the actionable mutations analysis, we found 32 actionable mutations in 24 genes. Among them, NFKBIA and TP53 mutations was the most frequently, which were only identified in TCs. Additionally, TCGA database analysis found that the expression of NFKBIA mRNA in the TCs were significantly higher than thymomas. TET patients with high NFKBIA expression had shorter overall survival compared with patients with low/medium NFKBIA expression, thus providing insights to consider NFKBIA as a potential prognosis biomarker and therapeutic target in TETs.
2022-09-20 | Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence.
General transcription factor IIi (GTF2I) mutations are very common in thymic epithelial tumors (TETs) and are related to a more favorable prognosis in TET patients. However, limited research has been conducted on the role of GTF2I in the tumor immune microenvironment (TIME). Further, long non-coding RNAs (lncRNAs) have been associated with the survival of patients with TETs. Therefore, this study aimed to explore the relationship between GTF2I mutations and TIME and build a new potential signature for predicting tumor recurrence in the TETs. Research data was downloaded from The Cancer Genome Atlas database and the CIBERSORT algorithm was used to evaluate TIME differences between GTF2I mutant and wild-type TETs. Relevant differentially expressed lncRNAs based on differentially expressed immune-related genes were identified to establish lncRNA pairs. We constructed a signature using univariate and multivariate Cox regression analyses. GTF2I is the most commonly mutated gene in TETs, and is associated with an increased number of early-stage pathological types, as well as no history of myasthenia gravis or radiotherapy treatment. In the GTF2I wild-type group, immune score and immune cell infiltrations with M2 macrophages, activated mast cells, neutrophils, plasma, T helper follicular cells, and activated memory CD4 T cells were higher than the GTF2I mutant group. A risk model was built using five lncRNA pairs, and the 1-, 3-, and 5-year area under the curves were 0.782, 0.873, and 0.895, respectively. A higher risk score was related to more advanced histologic type. We can define the GTF2I mutant-type TET as an immune stable type and the GTF2I wild-type as an immune stressed type. A signature based on lncRNA pairs was also constructed to effectively predict tumor recurrence.
2022-04-22 | Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
2022-04-19 | Construction of immune-related LncRNAs classifier to predict prognosis and immunotherapy response in thymic epithelial tumors
The primary objective of this study was to construct an immune-related long noncoding RNAs (IRLs) classifier to precisely predict the prognosis and immunotherapy response of patients with thymic epithelial tumors (TET). Based on univariable Cox regression analysis and Lasso regression, six prognosis-related IRLs (AC004466.3, AC138207.2, AC148477.2, AL450270.1, HOXB-AS1 and SNHG8) were selected to build an IRL classifier. Importantly, results of qRT-PCR validated that higher expression levels of AC138207.2, AC148477.2, AL450270.1 and SNHG8 as well as lower expression levels of AC004466.3, and HOXB-AS1 in TETs samples compared with normal controls. The IRL classifier could effectively classify patients into the low-risk and high-risk groups based on the different survival parameters. In terms of predictive ability and clinical utility, the IRL classifier was superior to Masaoka staging system. Additionally, IRL classifier is significantly associated with immune cells infiltration (dendritic cells, activated CD4 memory T cells and tumor-infiltrating lymphocyte (TIL), T cell subsets in particular), immune microenvironment (immune score and immune checkpoint inhibitors) and immunogenicity (TMB) in TETs, which hints that IRL classifier is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for TETs patients. Encouragingly, according to TIDE algorithm, there were more immunotherapy responders in the low-risk IRL subgroup and the IRL score was robustly negatively linked to the immunotherapeutic response. To sum up, the IRL classifier was established, which can be used to predict the prognosis, immune infiltration status, immunotherapy response in TETs patients, and may facilitate personalized counseling for immunotherapy.
2022-01-28 | Downregulation of DNMT3a expression by RNAi and its effect on NF-κBs expression of thymic epithelial cells.
To understand the characteristics of DNA methyltransferase 3a (DNMT3a) in thymoma associated Myasthenia Gravis reveal its transcriptional regulator network as while as analyze the effect of DNMT3a on Rel/ nuclear factor-kappaB family (RelA/RelB) and its downstream autoimmune regulatory factor (Aire). Tissues of 30 patients with thymoma, with or without myasthenia gravis (MG), were collected and the DNMT3a protein expression were evaluated through immunohistochemistry. We performed mRNA expression profiling microarray detection and analysis, and integrated the analysis by constructing protein-protein interaction networks and the integration with other database. We identified molecular difference between low and high DNMT3a in the thymoma by heatmap. We also performed PCR validation in thymoma tissues. The DNMT3a-shRNA plasmid was transfected into TEC cells, and these cells were treated with 5-aza-2-deoxycytidine, a blocker of DNMT3a. After the down-regulation of DNMT3a in TEC cells, the transcript and protein levels of RelA, RelB, Aire, and CHRNA3 were evaluated by western blotting. In addition, changes in gene expression profiles were screened through microarray technology. We performed differential gene analysis in the thymoma cohort by heatmap with R (v.4.3.0) software. In 30 matched tissue specimens, the expression of DNMT3a protein in thymoma with MG was lower than that in thymoma. Through mRNA expression profiling analysis, we constructed a co-expression network of DNMT3a and found direct interaction between IKZF1 and DNMT3a, and this co-expression relationship was overlappted with Cistrome DB database. We found up-regulation of 149 mRNAs and repression of 177 mRNAs in thymoma with MG compared with thymoma. Gene ontology and pathway analysis show the involvement of a multitude of genes in the mis-regulation of MG-related pathways. RNA interference significantly reduced the level of mRNA of DNMT3a, which proved that plasmid DNMT3a was effective. In comparison to the control group, the levels of DNMT3a, Aire, and CHRNA3 mRNA and protein in TEC cells transfected with DNMT3a-shRNA interference plasmid were significantly decreased, while the expression level of RelA and RelA/RelB was significantly increased. Our study reveals the DNMT3a-NF-κB pathway has a major effect on MG, and can be used as a marker for diagnosis as well as a target for MG treatment.
antibodies
2026-08-16 | Is phrenic nerve-sparing worthwhile for phrenic-involved thymic epithelial tumors? A retrospective cohort study.
To determine whether phrenic nerve (PN) sparing offers a worthwhile trade-off between functional preservation and oncologic safety compared with resection in PN-involved thymic epithelial tumors (TETs), and to establish an objective tool for postoperative respiratory risk stratification. In this retrospective cohort of patients with TETs with PN invasion, 122 propensity score-matched cases were analyzed from 2016 to 2024. PN preservation or resection was determined intraoperatively based on the extent of invasion. The diaphragmatic elevation (DE) ratio was calculated as [(preoperative diaphragm-apex distance - postoperative distance)/preoperative distance] × 100% according to X-rays, and cutoff values were defined by respiratory complication risk. Perioperative and oncologic outcomes were compared between the PN-sparing and PN resection groups. Overall perioperative morbidity and recovery outcomes were comparable between the PN-sparing and PN-resection groups; however, tumor progression was significantly more frequent on the PN-sparing group (39.3% vs 23.0%), resulting in worse progression-free survival (PFS) (P = .027), although overall survival (OS) remained comparable in the 2 groups. Multivariable analysis identified PN preservation as an independent predictor of progression (P = .049). Furthermore, our receiver operating characteristic-derived DE classification scheme (mild, ≤15%; moderate, 15-25%; severe, ≥25%) predicted severe postoperative respiratory complications (P < .001). PN resection improves PFS without increasing severe perioperative complications, although OS is comparable to that with PN-sparing.
2026-07-21 | Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026—A Narrative Review
Palliative systemic therapy for advanced thymic epithelial tumors (TET) is challenging due to scarce evidence and biological heterogeneity. Scientific discussion, as in this review, is limited to cross-trial comparisons of small, non-randomized studies. Platinum-based combination chemotherapy is the standard first-line treatment. Here, we challenge the addition of anthracyclines to platinum in thymoma. We critically appraise new combinations with antiangiogenic drugs and immune checkpoint inhibitors (ICI) in thymic carcinoma and their implications for therapy sequences. We review the data on classic genomics-based targeted therapy that does not benefit most patients and explore established and upcoming biomarkers including KIT and HER2. Finally, we discuss investigational therapies like anti-TROP2 antibody-drug conjugates and proteasome inhibitors, as well as topics and design of future research.
2026-07-11 | Identification of CCL4-positive macrophages and their associated immune microenvironment in thymic epithelial tumors
Thymic epithelial tumors (TETs) are one of the primary tumor types in the mediastinum, originating from thymic epithelial cells. Recent studies have highlighted the close association between specific macrophage subpopulations and the tumor immunosuppressive microenvironment. However, the characteristics and immunological functions of macrophages within TETs are still poorly understood. Single-cell transcriptome sequencing and the TCGA-THYM data were collected for integrated analysis of macrophage characteristics. The target cells were verified using multiplex immunofluorescence (mIF) staining. Functional validation was performed using Western blot and Transwell migration assays. Drug sensitivity was evaluated by predicting the half-maximal inhibitory concentration through oncoPredict. A group of CCL4 + macrophage subpopulations was clustered from the TETs myeloid single-cell subpopulation. By cell communication analysis, CCL4 + macrophages were positively correlated with exhausted T cells and regulatory T cells (Tregs). mIF staining confirmed a significant positive association between CCL4 + CD163 + cells and FOXP3 + CD4 + cells in terms of their proportions (r = 0.679, p < 0.001). Furthermore, in vitro experiments demonstrated that macrophages promoted Treg migration, which was significantly reduced by CCL4 blockade ( p < 0.05). Additionally, there are significant differences in drug sensitivity predictions and survival between TET patients with high and low CCL4 expression. These findings suggest that CCL4 + macrophages are specifically present in TETs and are related to the immune microenvironment of Treg infiltration.The expression of CCL4 in other immune cell subpopulations and cohorts still needs further verification to clarify its unique role in TET macrophages.
2026-07-10 | Pathobiology of thymic epithelial tumours and the treatment strategy based on immuno-oncological characteristics: a narrative review.
Thymic epithelial tumours (TETs), including thymomas and thymic carcinomas, are relatively rare anterior mediastinal malignancies. Thymomas are well known to be associated with various autoimmune diseases, such as myasthenia gravis (MG), pure red cell aplasia, and hypogammaglobulinemia. The mainstay of treatment for all TETs is complete surgical resection, although recent advances in irradiation and anti-tumour drug therapies are increasingly indicated for advanced or recurrent disease. The pathobiology of TETs was reviewed to consider optimal treatment strategies based on their immuno-oncological characteristics. A comprehensive literature search was conducted using PubMed, focusing on the biology and treatment of TETs, along with integration of our original research data. Pathobiology is different between thymoma and thymic carcinoma. Incomplete T cell development is observed in thymoma, which may affect patient autoimmunity. Type AB, B1, and B2 thymomas harbour abundant immature T cells, which cannot act as effector T cells in treatment using immune checkpoint inhibitors (ICIs). Neoplastic thymic epithelial cells (TECs) express programmed cell death-ligand 1 (PD-L1) at varying levels, and frequent genetic aberrations are observed according to the World Health Organization (WHO) classification. Germinal centre formation in the surrounding thymus may have a clinical role in thymoma-associated MG. Regarding treatment strategies, radical minimally invasive thymectomy using robotic technology is now available for MG. Effective molecular-targeted and ICI therapies have recently been introduced, and further novel targeted therapies are currently under development. WHO histological subtypes and inflammatory biomarkers are practically useful for determining the treatment strategy. A fundamental understanding of pathobiology and immuno-oncology is crucial for the appropriate management of TETs.
2026-07-10 | Systemic therapy for advanced thymic epithelial tumors: a narrative review of current evidence and perspectives.
Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare tumors. Although systemic therapy is commonly used for unresectable advanced or recurrent TETs, establishing robust evidence remains challenging. This narrative review summarizes current evidence and incorporates the latest clinical trial data, reporting outcomes separately for thymoma and thymic carcinoma whenever possible. We also highlight practical considerations relevant to clinical practice, including dosing strategies and toxicity management. We searched PubMed and Google Scholar for prospective and retrospective original studies, meta-analyses, review articles, and case studies published up to November 2025 using terms including "thymoma", "thymic carcinoma", "thymic cancer", "thymic tumors", "thymic epithelial tumors", "chemotherapy", "systemic treatment", "immunotherapy", and "targeted therapy". Ongoing trials were identified via ClinicalTrials.gov and the Japan Registry of Clinical Trials. Retrospective studies enrolling fewer than 15 participants were excluded. Systemic therapy for advanced TETs continues to include cytotoxic chemotherapy as a major component. In selected settings, particularly in thymic carcinoma, targeted therapy and immune checkpoint inhibitors (ICIs) represent additional active options. Emerging trials suggest that combination strategies may enhance efficacy. Novel drugs, including bispecific antibodies and antibody-drug conjugates, are being evaluated in ongoing phase II trials. Despite the rarity of TETs, systemic treatment options have gradually expanded through the accumulation of evidence from small phase II studies. Future advances will require collaborative prospective trials to validate predictive biomarkers and support biomarker-enriched trial designs.
proteins
2025-05-28 | Leveraging AI predictive models to develop thymic tumor–specific peptides mimicking COL17A1 alterations.
e20138 Background: We recently identified COL17A1 protein as a novel target in thymic epithelial tumors (TETs). Here, we designed tumor-specific peptides to mimic mutation regions in COL17A1. These peptides are intended as tools to generate antibodies targeting mutation-specific epitopes on COL17A1. Methods: In TCGA dataset, E391Kfs12, V809A, and P1409L alterations were frequently observed in the COL17A1 gene across various tumors, including TETs. The COL17A1 sequence was retrieved from UniProt, and mutations were introduced individually and in combination into the sequence. BLAST alignment analysis enabled direct comparison between the wild type and altered amino acid sequences. Next, we developed peptides of 8-10 Amino Acid (AA) around each mutation. We assessed the biophysical properties, immunogenicity (NetMHCpan), B-cell epitope prediction (Kolaskar), surface accessibility (Emini), solubility (NetSolP), thermal stability (TempStatPro) and enzyme function (TFPC). AlphaFold-3 analyzed predicted Template Modeling (pTM) and Local Distance Difference Test (pLDDT) scores for global folding and local stability, respectively. Results: Among the mutations, E391Kfs12 was located intracellularly, while V809A, and P1409L were extracellular. Using MutaGene, P1409L & E391Kfs12 were functionally deleterious. Next, a total of 144 peptides were designed to mimic mutations, including single and combined alteration. COL17A1 peptides had stronger binding affinity to MHC class I compared to class II. HLA-A24:02 & HLA-A26:01 (Score-BA 0.01) the strongest peptide-HLA-I affinity. The T-cell Immunogenicity predictions indicated the highest score for peptides near P1409L (Max 0.1). Emini surface accessibility showed the highest cell surface expression for E391Kfs12 (2.03) and P1409L (1.89). Epitope Conservancy Analysis evaluated matches with target and related sequences, with P1409L achieving the best score of 80% (range 55%–90%). Next, we divided peptides into 6 groups based on mutation sites. We assessed pLDDT (0–100), where high scores indicate strong local structural confidence. Single peptides had pLDDT >90, while most grouped peptides had scores <70. Peptides mimicking E391Kfs12 showed highest solubility (mean: 0.64, 0.60–0.78) and strong thermal stability at 45°C. P1409L peptides exhibited high enzymatic activity (mean: 0.48) but lower thermal stability (>70°C). V809A peptides demonstrated intermediate solubility (mean: 0.54) and stability, requiring optimization. Conclusions: AI predictive models enabled the design of thymic-tumor-specific peptides mimicking COL17A1 alterations. E391Kfs12 peptides with superior solubility and stability, and P1409L peptides, with strong immunogenicity, are promising candidates for antibody epitope generation. These findings provide a foundation for developing mutation-specific antibodies targeting thymic epithelial tumors.
2023-10-31 | MA08.05 Combining SBRT with GM-CSF and Peg-IFNα to Induce Abscopal Effects in Previously Treated Patients with Stage IV Thymic Tumors
After the failure of multi-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis.
2022-07-19 | A Proposed Link Between Acute Thymic Involution and Late Adverse Effects of Chemotherapy.
Epidemiologic data suggest that cancer survivors tend to develop a protuberant number of adverse late effects, including second primary malignancies (SPM), as a result of cytotoxic chemotherapy. Besides the genotoxic potential of these drugs that directly inflict mutational burden on genomic DNA, the precise mechanisms contributing to SPM development are poorly understood. Cancer is nowadays perceived as a complex process that goes beyond the concept of genetic disease and includes tumor cell interactions with complex stromal and immune cell microenvironments. The cancer immunoediting theory offers an explanation for the development of nascent neoplastic cells. Briefly, the theory suggests that newly emerging tumor cells are mostly eliminated by an effective tissue immunosurveillance, but certain tumor variants may occasionally escape innate and adaptive mechanisms of immunological destruction, entering an equilibrium phase, where immunologic tumor cell death "equals" new tumor cell birth. Subsequent microenvironmental pressures and accumulation of helpful mutations in certain variants may lead to escape from the equilibrium phase, and eventually cause an overt neoplasm. Cancer immunoediting functions as a dedicated sentinel under the auspice of a highly competent immune system. This perspective offers the fresh insight that chemotherapy-induced thymic involution, which is characterized by the extensive obliteration of the sensitive thymic epithelial cell (TEC) compartment, can cause long-term defects in thymopoiesis and in establishment of diverse T cell receptor repertoires and peripheral T cell pools of cancer survivors. Such delayed recovery of T cell adaptive immunity may result in prolonged hijacking of the cancer immunoediting mechanisms, and lead to development of persistent and mortal infections, inflammatory disorders, organ-specific autoimmunity lesions, and SPMs. Acknowledging that chemotherapy-induced thymic involution is a potential risk factor for the emergence of SPM demarcates new avenues for the rationalized development of pharmacologic interventions to promote thymic regeneration in patients receiving cytoreductive chemotherapies.
2019-11-22 | Follistatin impacts Tumor Angiogenesis and Outcome in Thymic Epithelial Tumors
Abstract Tumor angiogenesis is a key factor in the progression of thymic epithelial tumors (TETs). Activin A, a member of the TGFβ family, and its antagonist Follistatin are involved in several human malignancies and angiogenesis. We investigated Activin A and Follistatin in serum and tumor tissue of patients with TETs in relation to microvessel density (MVD), WHO histology classification, tumor stage and outcome. Membranous Activin A expression was detected in all tumor tissues of TETs, while Follistatin staining was found in tumor nuclei and cytoplasm. Patients with TETs presented with significantly higher Activin A and Follistatin serum concentrations compared to healthy volunteers, respectively. Follistatin serum concentrations correlated significantly with tumor stage and decreased to physiologic values after complete tumor resection. Follistatin serum concentrations correlated further with MVD and were associated with significantly worse freedom from recurrence (FFR). Low numbers of immature tumor vessels represented even an independent worse prognostic factor for FFR at multivariable analysis. To conclude, the Activin A - Follistatin axis is involved in the pathogenesis of TETs. Further study of Follistatin and Activin A in TETs is warranted as the molecules may serve as targets to inhibit tumor angiogenesis and tumor progression.
2019-04-01 | WT1 as an immunotherapy target for thymic epithelial tumors: a novel method to activate anti-tumor immunity
Thymic epithelial tumors (TETs) are family of rare cancers that exhibit diverse histology and variable clinical behavior (1). A significant fraction of patients, especially those with thymic carcinoma, have locally-advanced or metastatic disease at diagnosis that is often unresectable (1). Chemotherapy is associated with objective response rates (ORR) of 50–90% in the front-line setting, but limited benefit is observed in patients with recurrent disease (1,2). With few exceptions, biological agents have not demonstrated clinically meaningful activity in relapsed or refractory TETs (3). A low tumor mutation burden and paucity of actionable biological targets creates challenges for the development of targeted therapies for TETs (4,5). Hence, there is a pressing need to develop new treatments, especially for patients with advanced thymic carcinomas.
small molecules
2026-07-09 | PRRC2A-mediated m6A modification on NCOA4 promotes thymic epithelial tumor progression through PKM2-induced glycolysis.
Thymic epithelial tumors (TETs) are heterogeneous neoplasms. While most early-stage cases are curable after resection, advanced or aggressive subtypes have limited treatment options and poor outcomes. The molecular mechanisms underlying their metabolic reprogramming remain poorly understood. Proline-rich Coiled-coil 2a (PRRC2A), a N6-methyladenosine (m6A) reader protein, is significantly upregulated in TET tissues and is associated with poor clinical outcomes. Multi-omics analyses and molecular experiments revealed that PRRC2A binds to m6A-modified sites within the NCOA4 mRNA, thereby stabilizing NCOA4 transcripts and enhancing its protein expression. Elevated NCOA4 interacts with PKM2, a rate-limiting glycolytic enzyme, resulting in increased glycolysis and promoting TETs progression. In vivo experiments showed that inhibition of PRRC2A suppressed tumor growth and metastasis in TETs, while combined treatment with the PKM2 inhibitor C599 and PRRC2A knockdown produced enhanced antitumor effects. These findings provide novel insights into the glycolytic metabolic regulation of TETs and suggest that the PRRC2A-NCOA4-PKM2 axis represents a promising therapeutic target.
2026-07-01 | 153P Efficacy and safety of lenvatinib in patients with thymic epithelial tumors: A retrospective, multicenter study
Thymic epithelial tumors (TETs) are rare malignancies with limited options after standard platinum-based chemotherapy. While the REMORA trial confirmed the efficacy of lenvatinib, a multi-targeted tyrosine kinase inhibitor (TKI), in thymic carcinoma (TC) patients with progressive disease, data for broader TET subtypes remain scarce. This study evaluated lenvatinib's efficacy and safety in patients with TETs, including TC and advanced malignant thymoma.
2026-06-26 | Redefining therapeutic horizons in thymic epithelial tumors: precision, combinations, and emerging biology
Thymic epithelial tumors (TETs) are rare and diverse cancers with distinctive immune features, limited prospective evidence, and few systemic options. Their association with autoimmunity, especially thymomas, complicates treatment decisions. This review examines molecular profiling and predictive biomarkers in TET and explores new treatment strategies. We highlight priorities for future trials, global registries, and real-world data to expand access to expert, multidisciplinary care, charting a path toward precision-guided, combination-based treatments.
2026-06-26 | Platinum-Based Chemotherapy with Novel Systemic Therapies in Patients with Unserectable or Metastatic Thymic Epithelial Tumors: A Systematic Review and Single-Arm Meta-Analysis
All articles of this category (opens in new window) Address for correspondence Gabriela Barbosa Silva (gabrielabarbosa20161@hotmail.com) Introduction: Thymic epithelial tumors (TETs) are rare malignancies with poor prognosis and limited evidence guiding systemic treatment in advanced stages. Following progression on platinum-based chemotherapy, no standard second-line treatment has been established. In recent years, immune checkpoint inhibitors (ICIs) and anti-angiogenic agents have been investigated in combination with chemotherapy to enhance therapeutic efficacy. However, the benefit of these combinations remains unclear. Objective: To evaluate the efficacy of platinum-based chemotherapy combined with novel systemic therapies as a first-line treatment for advanced TETs . Methods: A systematic search of PubMed, Embase, and Cochrane databases was conducted for studies involving histologically confirmed thymoma or thymic carcinoma with unresectable, locally advanced, recurrent, or metastatic disease, treated in the first-line setting with platinum-based doublets plus ICIs or anti-angiogenic agents. Studies on early-stage, resectable tumors, monotherapy regimens, or prior systemic therapy were excluded. Meta-analyses were performed using a random-effects model. Heterogeneity was assessed with the I² statistic and Cochran’s Q test. Sensitivity and subgroup analyses were conducted using meta-analyses of proportions. Results: Of 762 records screened, five phase II trials and four cohort studies met the inclusion criteria, comprising 206 patients (93.7% thymic carcinoma, 6.3% thymoma). Pooled analysis showed a median duration of response of 12.32 months (95% CI: 5.43–27.93), a median progression-free survival of 13.69 months (95% CI: 8.45–22.19), and an objective response rate (ORR) of 58.9% (95% CI: 45.7–71.0). ORR was higher with anti-angiogenic agents 68.5% (95% CI: 52.5–81.0) than with ICIs 52.0%, (95% CI: 35.9–67.6; p = 0.1472). A statistically significant difference in partial response rates was observed between anti-angiogenic agents 68.5% and ICIs 46.9% (p = 0.0898). Conclusion: Despite the lack of randomized evidence, platinum-based chemotherapy combined with anti-angiogenic agents may represent a promising first-line strategy for patients with advanced TETs, particularly those with thymic carcinoma. Prospective evaluation is warranted to validate these results. Publication History Article published online: 26 June 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil Bibliographical Record Gabriela Barbosa Silva, Lorrany Rodrigues Costa, Bianca Gonzaga Freitas, Letícia Peixoto Gomes, Filipe Luís Vasconcelos Visani. Platinum-Based Chemotherapy with Novel Systemic Therapies in Patients with Unserectable or Metastatic Thymic Epithelial Tumors: A Systematic Review and Single-Arm Meta-Analysis. Brazilian Journal of Oncology 2026; 22. DOI: 10.1055/s-0046-1825474
2026-05-28 | Surufatinib for advanced or metastatic chemotherapy-refractory thymic epithelial tumor: A single-arm, single-center, phase II study.
8119 Background: Thymic epithelial tumors (TETs), though relatively rare, represent the most common anterior mediastinal malignancy in adults. Platinum-based regimens are the standard first-line therapy; however, treatment options for subsequent lines remain poorly defined. Surufatinib, an oral tyrosine kinase inhibitor targeting VEGFR1/2/3, FGFR1, and CSF-1R, exerts both anti-angiogenic and immune-modulating effects. This study aimed to evaluate the efficacy and safety of surufatinib in patients (pts) with type B2/B3 thymoma (TM) or thymic carcinoma (TC), providing a potential new therapeutic strategy for TETs following anthracycline/taxane-based therapy. Here, we report the initial results. Methods: This was a single-arm, prospective phase II study. Eligible pts had histologically or cytologically confirmed, unresectable or radiotherapy-ineligible, advanced recurrent or metastatic B2/B3 TM or TC, with progression following at least one prior platinum-based chemotherapy regimen. Pts were aged >18 years and had at least one measurable lesion per RECIST 1.1 criteria. Treatment consisted of surufatinib 300 mg orally once daily in a 4-week cycle. Tumor assessments were conducted every 8 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Results: As of December 25, 2025, 20 pts were enrolled and evaluated. The median age was 55.5 years (range: 35–69), with 55% being male. Pathological subtypes included B2 TM (30%), B3 TM (15%), and thymic squamous cell carcinoma (TSCC, 55%). Eighteen pts (90%) presented with >5 metastatic sites. Ten pts (50%) achieved a partial response, and ten pts (50%) achieved stable disease. The ORR was 50%, and the DCR was 100%. With a median follow-up of 9.50 months, the median PFS was 11.9 months, and the 9-month PFS rate was 73.5%. Median OS was not reached, with an 18-month OS rate of 91.7%. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (70%), diarrhea (40%), elevated bilirubin (40%), and elevated transaminases (25%). Grade 3 TRAEs included hypertension (15%), diarrhea (5%), and elevated transaminases (5%). No treatment-related deaths were reported. Conclusions: Surufatinib monotherapy demonstrated promising antitumor activity and a manageable safety profile in patients with previously treated, advanced recurrent or metastatic TETs, supporting further investigation in this population. Clinical trial information: ChiCTR2600116776.
cell therapies
2026-02-26 | When Central Tolerance Fails: Thymic Malignancies at the Intersection of Cancer Immunity and Autoimmunity
Thymic malignancies are rare cancers arising from thymic epithelial cells and are characterized by a highly diverse clinical phenotype, substantial histologic and morphologic heterogeneity, and frequent associations with autoimmune syndromes. Although the clinical, immunological, and cytoarchitectural changes associated with thymomas have been increasingly elucidated in the contemporary literature, very few studies have interrogated the direct role of tumor staging and histological grading in shaping autoimmunity burden and infection risk. In this narrative review, we synthesize contemporary clinical, immunological, and morphologic evidence linking thymic architecture and selection defects to the spectrum of paraneoplastic autoimmunity (MG, pure red cell aplasia, Good's syndrome) and to infectious vulnerability. We further appraise emerging therapeutic strategies, including immune checkpoint inhibition and adoptive cellular approaches, through a patient-stratified lens, emphasizing efficacy signals, immune-related adverse events, and practical considerations for selection and monitoring. We conclude by highlighting priorities for future investigation, including refining autoantibody signatures; mapping thymic microenvironments that drive tolerance failure, and prospectively evaluating stratified immunotherapeutic regimens that balance benefit with immune-mediated risk.
2026-01-07 | Oncological Outcomes of Complete Versus Limited Thymectomy in Early Stage Thymic Epithelial Tumors: A Systematic Review and Individual Patient Data Meta-Analysis
Objectives: To clarify the role of limited versus complete thymectomy in stage I thymic epithelial tumors (TETs) using standardized survival measures and predefined oncological outcomes. Methods: An individual patient data (IPD) meta-analysis of studies investigating complete versus limited thymectomy for stage I TETs was conducted. IPD was extracted from published Kaplan-Meier curves using the IPDfromKM method.Primary end point of the study was freedom from recurrence (FFR) in complete versus limited thymectomy. Secondary end points were time to progression (TTP), overall survival, recurrence rate in the overall population and stratified per Masaoka-Koga stage, and survival measures according to resection extension (thymomectomy alone versus hemi-thymectomy versus subtotal thymectomy).Hazard ratios and relative 95% confidence intervals (95% CIs) were estimated with Cox regression analyses. Odds ratio (OR) with 95% CI was used to derive categorical variables. Results: = 0.02).Finally, in those receiving limited thymectomy, thymomectomy alone had the worst FFR. Conclusion: No evidence favored limited than complete thymectomy in early stage TET treatment according to standardized survival measures. However, in Masaoka-Koga stage II disease, complete thymectomy demonstrated lower recurrence rate. Finally, among patients receiving limited thymectomy, thymomectomy alone leads to worse prognosis.
2025-10-09 | Total thymectomy is oncologically superior to partial thymectomy in patients with thymic carcinoma: insights from a multicenter real-world data analysis
Background: Although total thymectomy has been the standard surgical approach for thymic epithelial tumors, an increasing number of recent reports suggest that partial thymectomy for early-stage thymomas may yield outcomes comparable to those of total thymectomy. However, whether partial thymectomy is a viable alternative for thymic carcinoma remains unclear. Materials and Methods: A total of 106 patients with thymic carcinoma underwent curative intended resection at 19 institutions between January 2010 and December 2021. Excluding 14 patients with incomplete resection, 92 patients with thymic carcinoma who underwent total (n = 73) or partial thymectomy (n = 19) were compared. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Overlap weighting was applied to adjust for potential confounding factors. Results: Among patients with clinical-stage I disease, 79.3% were upstaged to stage II or higher postoperatively. Unadjusted analyses revealed no statistically significant differences in OS and RFS between the total and partial thymectomy groups, although a trend toward poorer outcomes in the partial thymectomy group was observed. After overlap weighting, partial thymectomy was associated with significantly poorer OS (p = 0.0027) and higher recurrence risk (p < 0.0001). Early postoperative recurrence occurred more frequently in the partial thymectomy group. Conclusion: Partial thymectomy was associated with significantly worse survival and recurrence outcomes in thymic carcinoma. Given the limitations of preoperative diagnosis, total thymectomy should remain the preferred surgical approach for undiagnosed thymic epithelial tumors to achieve optimal oncologic control and minimize the risk of recurrence.
2025-04-10 | <i>De novo</i> Thymus Reconstitution: The Rising of Cell-based Strategies
The thymus plays a crucial role in the generation of functional T cells, which are essential in adaptive immune responses. However, the involution, dysfunction, and even absence of the thymus induced by various factors such as aging, heredity, tumor, infection, and surgical removal, greatly impair or completely deprive the normal functions of the thymus and has been threatening the health of countless patients. Thus, reconstituting the thymus in these patients is remarkably necessary and urgent, in which thymus transplantation is viable, but the rare donors and related complications dramatically limit its clinical application. Other exogenous regeneration therapies, like sex steroid inhibition and cytokines treatments, usually have nonspecific, limited, and transient outcomes. By comparison, <i>de novo</i> cell-based strategies to reconstitute the thymus may be more feasible, which can generate fully functional thymuses usually using autologous cells without the dependence on limited thymus donors, thus avoiding transplant donor shortage as well as related complications, and overcome the defects of exogenous regeneration therapies. In this review, we summarized the progression in this field, including the generation of functional thymic epithelial cells (TECs), the clonogenic culture of TECs, stem cell treatment, and the construction of thymic organoids, to provide a global perspective for cell-based <i>de novo</i> thymus reconstitution.
2025-01-23 | Transplantation of the MSLN‐deficient Thymus Generates MSLN Epitope Reactive T Cells to Attenuate Tumor Progression
ABSTRACT The development of mesothelin (MSLN) epitope reactive T cells is observed in mice that are immunized with the MSLN vaccine. Engineered T cells expressing MSLN‐reactive high‐affinity TCR exhibit extraordinary therapeutic effects for invasive pancreatic ductal adenocarcinoma in a mouse model. However, the generation of MSLN‐reactive T cells through the introduction of MSLN ‐deficient thymus and the transplantation of the latter as a cure for cancer treatment have not been tested to date. In the present study, the expression of MSLN was mainly identified in medullary thymic epithelial cells (mTECs) but not in hematopoietic cells, cortical thymic epithelial cells (cTECs), endothelial cells, or fibroblast cells in the thymus. The increasement of activated T cells was observed in MSLN‐expressing tumors from MSLN ‐deficient mice, indicating that MSLN‐reactive T cells had developed. Finally, in an AOM‐DSS‐induced mouse model of colorectal cancer (CRC), transplantation of MSLN ‐deficient thymus repressed the progression of CRC, accompanied by an increased number of IFNγ‐expressing T lymphocytes in the tumors. The data from this study demonstrated that ectopic transplantation of MSLN ‐deficient thymus induced MSLN‐specific antitumor responses to MSLN‐expressing tumors, and thus attenuated tumor progression.
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2023-04-04 | Genomic characterization of thymic epithelial tumors reveals critical genes underlying tumorigenesis and poor prognosis.
Thymic epithelial tumors (TETs) are rare mediastinal tumors whose tumorigenesis mechanism is poorly understood. Characterization of molecular alterations in TETs may contribute to a better understanding of tumorigenesis and prognosis. Hybrid capture-based next-generation sequencing was performed on tumor tissues from 47 TETs (39 thymomas and 8 thymic carcinomas) to detect mutations in 315 tumor-associated genes. In total, 178 nonsynonymous mutations were identified, with a median of 3.79 per tumor in 47 TETs. Higher tumor mutation burden (TMB) level was more common in older TET patients, and significantly associated with the more advanced pathological type, especially in thymic carcinomas (TC) patients. The gene mutation profiles of B1-3, A/AB, and TC patients varied greatly. In the actionable mutations analysis, we found 32 actionable mutations in 24 genes. Among them, NFKBIA and TP53 mutations was the most frequently, which were only identified in TCs. Additionally, TCGA database analysis found that the expression of NFKBIA mRNA in the TCs were significantly higher than thymomas. TET patients with high NFKBIA expression had shorter overall survival compared with patients with low/medium NFKBIA expression, thus providing insights to consider NFKBIA as a potential prognosis biomarker and therapeutic target in TETs.
2022-09-20 | Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence.
General transcription factor IIi (GTF2I) mutations are very common in thymic epithelial tumors (TETs) and are related to a more favorable prognosis in TET patients. However, limited research has been conducted on the role of GTF2I in the tumor immune microenvironment (TIME). Further, long non-coding RNAs (lncRNAs) have been associated with the survival of patients with TETs. Therefore, this study aimed to explore the relationship between GTF2I mutations and TIME and build a new potential signature for predicting tumor recurrence in the TETs. Research data was downloaded from The Cancer Genome Atlas database and the CIBERSORT algorithm was used to evaluate TIME differences between GTF2I mutant and wild-type TETs. Relevant differentially expressed lncRNAs based on differentially expressed immune-related genes were identified to establish lncRNA pairs. We constructed a signature using univariate and multivariate Cox regression analyses. GTF2I is the most commonly mutated gene in TETs, and is associated with an increased number of early-stage pathological types, as well as no history of myasthenia gravis or radiotherapy treatment. In the GTF2I wild-type group, immune score and immune cell infiltrations with M2 macrophages, activated mast cells, neutrophils, plasma, T helper follicular cells, and activated memory CD4 T cells were higher than the GTF2I mutant group. A risk model was built using five lncRNA pairs, and the 1-, 3-, and 5-year area under the curves were 0.782, 0.873, and 0.895, respectively. A higher risk score was related to more advanced histologic type. We can define the GTF2I mutant-type TET as an immune stable type and the GTF2I wild-type as an immune stressed type. A signature based on lncRNA pairs was also constructed to effectively predict tumor recurrence.
2022-04-22 | Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
2022-04-19 | Construction of immune-related LncRNAs classifier to predict prognosis and immunotherapy response in thymic epithelial tumors
The primary objective of this study was to construct an immune-related long noncoding RNAs (IRLs) classifier to precisely predict the prognosis and immunotherapy response of patients with thymic epithelial tumors (TET). Based on univariable Cox regression analysis and Lasso regression, six prognosis-related IRLs (AC004466.3, AC138207.2, AC148477.2, AL450270.1, HOXB-AS1 and SNHG8) were selected to build an IRL classifier. Importantly, results of qRT-PCR validated that higher expression levels of AC138207.2, AC148477.2, AL450270.1 and SNHG8 as well as lower expression levels of AC004466.3, and HOXB-AS1 in TETs samples compared with normal controls. The IRL classifier could effectively classify patients into the low-risk and high-risk groups based on the different survival parameters. In terms of predictive ability and clinical utility, the IRL classifier was superior to Masaoka staging system. Additionally, IRL classifier is significantly associated with immune cells infiltration (dendritic cells, activated CD4 memory T cells and tumor-infiltrating lymphocyte (TIL), T cell subsets in particular), immune microenvironment (immune score and immune checkpoint inhibitors) and immunogenicity (TMB) in TETs, which hints that IRL classifier is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for TETs patients. Encouragingly, according to TIDE algorithm, there were more immunotherapy responders in the low-risk IRL subgroup and the IRL score was robustly negatively linked to the immunotherapeutic response. To sum up, the IRL classifier was established, which can be used to predict the prognosis, immune infiltration status, immunotherapy response in TETs patients, and may facilitate personalized counseling for immunotherapy.
2022-01-28 | Downregulation of DNMT3a expression by RNAi and its effect on NF-κBs expression of thymic epithelial cells.
To understand the characteristics of DNA methyltransferase 3a (DNMT3a) in thymoma associated Myasthenia Gravis reveal its transcriptional regulator network as while as analyze the effect of DNMT3a on Rel/ nuclear factor-kappaB family (RelA/RelB) and its downstream autoimmune regulatory factor (Aire). Tissues of 30 patients with thymoma, with or without myasthenia gravis (MG), were collected and the DNMT3a protein expression were evaluated through immunohistochemistry. We performed mRNA expression profiling microarray detection and analysis, and integrated the analysis by constructing protein-protein interaction networks and the integration with other database. We identified molecular difference between low and high DNMT3a in the thymoma by heatmap. We also performed PCR validation in thymoma tissues. The DNMT3a-shRNA plasmid was transfected into TEC cells, and these cells were treated with 5-aza-2-deoxycytidine, a blocker of DNMT3a. After the down-regulation of DNMT3a in TEC cells, the transcript and protein levels of RelA, RelB, Aire, and CHRNA3 were evaluated by western blotting. In addition, changes in gene expression profiles were screened through microarray technology. We performed differential gene analysis in the thymoma cohort by heatmap with R (v.4.3.0) software. In 30 matched tissue specimens, the expression of DNMT3a protein in thymoma with MG was lower than that in thymoma. Through mRNA expression profiling analysis, we constructed a co-expression network of DNMT3a and found direct interaction between IKZF1 and DNMT3a, and this co-expression relationship was overlappted with Cistrome DB database. We found up-regulation of 149 mRNAs and repression of 177 mRNAs in thymoma with MG compared with thymoma. Gene ontology and pathway analysis show the involvement of a multitude of genes in the mis-regulation of MG-related pathways. RNA interference significantly reduced the level of mRNA of DNMT3a, which proved that plasmid DNMT3a was effective. In comparison to the control group, the levels of DNMT3a, Aire, and CHRNA3 mRNA and protein in TEC cells transfected with DNMT3a-shRNA interference plasmid were significantly decreased, while the expression level of RelA and RelA/RelB was significantly increased. Our study reveals the DNMT3a-NF-κB pathway has a major effect on MG, and can be used as a marker for diagnosis as well as a target for MG treatment.
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Drug Discovery Landscape
4 orphan drug designations for Thymic epithelial neoplasm.
4 orphan drug designations for Thymic epithelial neoplasm.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant fully human IgG1 anti-PDL1 monoclonal antibody conjugated to a DNA topoisomerase I inhibitor | antibodies | FDA | 2025-10-16 | — | Shanghai Henlius Biotech, Inc. |
anti-human programmed cell death protein 1 linked to a human IgG4Fc and a human no-a-IL-2 mutein | antibodies | FDA | 2025-08-27 | — | Anwita Biosciences, Inc. |
humanized bispecific IgG1 antibody that can simultaneously bind to both programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4 | antibodies | FDA | 2020-09-02 | — | Jiangsu Alphamab Biopharmaceuticals Co., Ltd. |
milciclib maleate | small molecules | FDA | 2012-09-20 | — | Tiziana Life Sciences PLC |
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