Emerging innovative immunotherapies in malignant ascites: current landscape, challenges and perspectives

Abstract

Malignant ascites is a common, severe complication of advanced solid tumors, driven by multifactorial pathogenesis, including impaired lymphatic drainage, vascular endothelial growth factor-induced vascular hyperpermeability, pro-permeability inflammatory cytokines, and profound peritoneal immunosuppression. Clinically, it correlates with poor prognosis, reduced overall survival, and substantial quality-of-life deterioration. Current treatment remains predominantly palliative: repeated large-volume paracentesis offers transient symptom relief, fails to prevent reaccumulation, and carries procedural risks. Emerging evidence indicates malignant ascites is not merely passive fluid accumulation but an active, immunosuppressive niche shaped by bidirectional crosstalk among tumor cells, stromal components, diverse immune subsets (e.g., regulatory T cells, myeloid-derived suppressor cells, dysfunctional CD8 + T cells), and soluble mediators. This narrative review summarizes recent advances in immunomodulatory treatment for malignant ascites, with an emphasis on strategies targeting the ascitic immune microenvironment. Intraperitoneal administration of immune checkpoint inhibitors has shown acceptable safety and preliminary activity in early-phase single-arm trials, although confirmatory data from larger controlled studies are lacking. In randomized trials, the T-cell engager catumaxomab prolonged puncture-free survival, while the bispecific antibody M701 has shown similar benefits in a phase II randomized controlled study; these findings support further investigation of localized T-cell redirection. Preclinical and early-phase clinical studies suggest that intraperitoneal oncolytic viruses can induce immunogenic tumor cell death and T-cell activation, with single-cell analyses indicating remodeling of the ascitic immune microenvironment. Future directions include integrating ascites immune phenotyping, patient-derived organoids for drug sensitivity testing, and machine learning-based decision support to guide personalized immunotherapy.