2026-07-09 | Temporal Immune and Metabolic Shifts Drive the Anti-Tumor Efficacy of Resiquimod-Loaded Nanoparticles in Peritoneal Carcinomatosis.
Peritoneal carcinomatosis (PC) is an aggressive manifestation of advanced gynecological and gastrointestinal malignancies with high recurrence rates despite cytoreductive surgery and chemotherapy. We developed a cationic liposomal nanoparticle (DSTAP, ∼159 nm) to deliver and retain the toll-like receptor 7/8 agonist Resiquimod (R848) within the peritoneal cavity, aiming to modulate the tumor immune microenvironment (TIME) and improve therapeutic efficacy. DSTAP-R848 was evaluated in murine colorectal and ovarian PC models, alone or combined with oxaliplatin (Oxa). Survival, cure rates, and durable immunity following tumor rechallenge were assessed. Immune polarization was examined by incubating ascites and peritoneal fluid with naïve splenocytes, while flow cytometry and metabolomic profiling characterized intratumoral immune populations and metabolic changes. Combination therapy achieved cure rates of 80% in the colorectal model and 30% in the ovarian model, with no recurrence after rechallenge; Oxa monotherapy yielded no cures. Oxa+DSTAP-R848 increased CD8+ T cells and M1 macrophages, while reducing regulatory T cells and myeloid-derived suppressor cells. Immunosuppressive and glycolytic metabolites progressively declined, correlating with reduced tumor burden. Overall, DSTAP-R848 enhances chemotherapy efficacy by reshaping immune and metabolic pathways and promoting durable anti-tumor immunity in PC.
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2026-06-26 | Appendiceal Mucinous Neoplasms and Pseudomyxoma Peritonei: Current Classification and the Role of Intraperitoneal Chemotherapy.
Appendiceal mucinous neoplasms (AMNs) are a rare but clinically significant category of gastrointestinal tumors, ranging from low-grade appendiceal mucinous neoplasm (LAMN), the main precursor of pseudomyxoma peritonei (PMP), to high-grade appendiceal mucinous neoplasm (HAMN), poorly differentiated and signet-ring-cell adenocarcinomas, and goblet cell adenocarcinoma. Although current WHO and PSOGI classifications provide well established diagnostic criteria, controversies persist regarding the biological behavior and prognostic significance of the most aggressive subtypes and the relationship between HAMN and mucinous adenocarcinoma. While appendectomy is sufficient for localized LAMN, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is the treatment of choice for peritoneal dissemination This review integrates the histopathological and molecular classification of AMN and PMP with the evolution of intraperitoneal chemotherapy. Key findings indicate that KRAS and GNAS mutations are central drivers of mucin overproduction and peritoneal spread, that tumor grade and mucin cellularity remain the strongest prognostic determinants, and that the evidence supporting HIPEC and PIPAC derives largely from observational rather than randomized data. As a novel insight, we highlight the emerging role of patient-derived organoids as translational models for functional drug testing. Progress will depend on integrating molecular characterization, critical appraisal of intraperitoneal therapies, and organoid-based testing to advance individualized treatment for peritoneal surface malignancies.
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