Immunological Insights into Peritoneal Carcinomatosis for Gastrointestinal Malignancies: The Role of Soluble Factors in Malignant Ascites

Background and Objectives: Malignant ascites reflects the tumor microenvironment and provides valuable insights into peritoneal metastasis. This study aimed to assess soluble immune system-related molecules in the ascites fluid of advanced gastrointestinal cancer patients with peritoneal carcinomatosis and to explore potential therapeutic opportunities. Methods: This multicenter prospective cohort study included 48 patients with gastrointestinal adenocarcinoma (17 colorectal, 16 gastric, and 15 pancreatic) with malignant ascites and 15 patients for comparison who required benign ascites drainage for advanced heart failure. Blood samples for routine parameters and ascites fluid for cytokine and soluble immune checkpoint analysis were collected. Parameters were compared between cancer patients and the comparison group, across cancer subgroups, and in correlation with survival. Results: The mean age of participants was 60.2 ± 14.9 years, with a female-to-male ratio of 11:20. The median survival of cancer patients was 84.0 days. Compared with heart failure-associated transudative ascites, malignant ascites demonstrated higher levels of TNF-α, IL-6, IL-10, IL-12p70, IL-18, IL-23, s4-1BB, and TGF-β1, while albumin levels were lower. Significant intergroup differences were observed in TNF-α, IL-6, IL-8, IL-10, IL-12p70, IL-23, 4-1BB, TGF-β1, and PD-L1 levels. In exploratory multivariable analysis, IL-10 and soluble 4-1BB emerged as potential predictors of shorter survival, although these findings require validation in larger cohorts. Survival was negatively correlated with PD-L1, TNF-α, IL-6, and IL-10 in colorectal cancer; 4-1BB, TGF-β1, IL-8, and IL-10 in gastric cancer; and TGF-β1, IL-6, and IL-10 in pancreatic cancer. Conclusions: These exploratory findings indicate that the immunosuppressive milieu in malignant ascites in gastrointestinal cancers may be mediated by cancer subtype-specific pathways, warranting further mechanistic and translational investigation.