Hyperthermia combined with intraperitoneal perfusion of drugs improves malignant ascites caused by gastrointestinal tumors by reshaping the tumor immune microenvironment.

Malignant ascites treatment remains challenging. Hyperthermia is a promising adjunct to intraperitoneal therapies, but its mechanisms are unclear. We aimed to investigate whether combining hyperthermia with endostatin and cisplatin alleviates malignant ascites by reprogramming immune microenvironment. A total of 28 patients with malignant ascites were enrolled and divided into three groups: untreated, recombinant human endostatin plus cisplatin, and hyperthermia combined with recombinant human endostatin and cisplatin. Ascites volume was monitored by B-ultrasound. VEGF, IL-10, and IFN-γ levels in ascitic fluid were measured via ELISA. Immune cell proportions and macrophage polarization were analyzed by flow cytometry. A murine malignant ascites model was established. Mice were treated according to same therapeutic groupings. Tumor burden was assessed via in vivo fluorescence imaging, ascites volume measurement, body weight changes, and survival analysis. Cytokine levels and macrophage polarization in murine ascites were also evaluated. Hyperthermia combined with endostatin and cisplatin reduced ascites volume and modulated ascitic microenvironment in patients with malignant ascites. Triple therapy of hyperthermia, endostatin, and cisplatin functioned dually to eliminate pro-tumoral leukocytes in ascites and reprogram macrophages into M1 phenotypes. Hyperthermia synergized with endostatin and cisplatin to suppress malignant ascites progression, mitigate systemic toxicity, and extend survival in mice. Triple therapy modulated ascitic microenvironment and promoted macrophage M1 polarization in a murine malignant ascites model. Macrophage ablation abolished therapeutic efficacy of triple therapy in malignant ascites mice. The combined strategy of hyperthermia, endostatin, and cisplatin suppresses malignant ascites in gastrointestinal cancer through inducing M1 macrophage polarization.