Malignant ascites as an immune organ and implications for cancer immunotherapy

Malignant ascites is a devastating complication of several advanced malignancies. Beyond serving as a poor prognostic indicator, the rapid accumulation of ascitic fluid imposes a significant symptom burden that can severely worsen quality of life. Although immunotherapy has revolutionized solid tumor oncology, these approaches have shown only limited benefit in the treatment of malignant ascites. Here, we summarize landmark clinical trials exploring immunotherapy as a potential treatment of malignant ascites. We then conceptualize malignant ascites as a functionally distinct immunologic compartment rather than a passive fluid reservoir, highlighting unique immunologic features that may underlie the challenges in translating immunotherapy to this context. By advancing our collective understanding of this unique immune microenvironment, it may become possible to develop rational combination strategies that provide symptomatic relief and meaningfully improve quality of life for patients with end-stage disease.