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

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

  • Free Radic Biol Med. 2025 Feb 4:230:177-189. doi: 10.1016/j.freeradbiomed.2025.02.002.
Miao Qi 1,  Xinyi Zhao 2,  Runze Fan 3,  Jiao Lin 3,  Zhuo Li 3,  Na Liu 4,  Xuejun Sun 5,  Dehui Xu 6,  Jianbao Zheng 7,  Dingxin Liu 8,  Renwu Zhou 3,  Mingzhe Rong 3,  Kostya Ken Ostrikov 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Electrical Insulation and Power Equipment, Centre for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an, 710049, PR China; School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, PR China.
  • 2 School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, PR China.
  • 3 State Key Laboratory of Electrical Insulation and Power Equipment, Centre for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an, 710049, PR China.
  • 4 Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Medical Science Center, Xi'an Jiaotong University, Xi'an, 710061, PR China.
  • 5 Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, PR China.
  • 6 State Key Laboratory of Electrical Insulation and Power Equipment, Centre for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an, 710049, PR China; School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, PR China; Department of Dermatology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, PR China. Electronic address: dehuixu@mail.xjtu.edu.cn.
  • 7 Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, PR China. Electronic address: bobzheng@xjtu.edu.cn.
  • 8 State Key Laboratory of Electrical Insulation and Power Equipment, Centre for Plasma Biomedicine, Xi'an Jiaotong University, Xi'an, 710049, PR China. Electronic address: liudingxin@mail.xjtu.edu.cn.
  • 9 Centre for Materials Science, and Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, QLD, 4000, Australia.
PMID: 39914684 DOI: 10.1016/j.freeradbiomed.2025.02.002
Abstract

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.

Keywords

Hyperthermic intraperitoneal perfusion; Immunotherapy; Peritoneal carcinomatosis; Plasma-activated saline; Pyroptosis.

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