Plasma-activated saline hyperthermic perfusion-induced pyroptosis boosts peritoneal carcinomatosis immunotherapy.

Peritoneal carcinomatosis (PC) is a common metastatic cancer with limited treatment options. Herein, we present a novel strategy for the combined treatment of PC involving plasma-activated saline (PAS) and hyperthermic intraperitoneal perfusion. PAS revealed a strong cytotoxic effect because of reactive oxygen species (ROS) in two-dimensional cultures and three-dimensional tumor spheroids of PC-related cell lines. Notably, PAS induced Gasdermin E (GSDME)-dependent pyroptosis and immunogenic cell death in vitro. PAS-enhanced hyperthermic intraperitoneal perfusion (PE-HIP) increased the number of CD3+, CD4+ and CD8+ T cells, while decreased the number of regulatory T cells, indicating that PAS stimulated T cell-based immune responses in vivo. Moreover, PE-HIP significantly inhibited tumor growth and improved survival in a PC-mice model, with no significant toxic side effects. Meanwhile, vaccination with PAS-induced cell pyroptosis activated systemic antitumor immunity to prevent subcutaneous tumor growth. Overall, PE-HIP can serve as a new approach for PC treatment by ROS-assisted cancer immunotherapy.