From local eradication to immune priming: Paradigm shift of hyperthermic intraperitoneal chemotherapy in gastric cancer therapy

Abstract

Patients with locally advanced (pathological T4) gastric cancer remain at high risk for peritoneal recurrence despite curative surgery. Although hyperthermic intraperitoneal chemotherapy (HIPEC) reduces this risk, its inconsistent impact on overall survival has prevented its routine use. However, a recent study by Lian et al, published in World Journal of Gastroenterology, demonstrates that postoperative HIPEC improves disease-free survival and peritoneal control without severe toxicity, renewing interest. We propose a paradigm shift: The value of HIPEC lies not in cytoreduction but in its function as a potent immunogenic stimulus. By inducing immunogenic cell death, HIPEC converts residual tumor cells into an in situ vaccine. This releases tumor antigens, activates antigen-presenting cells, and catalyzes a systemic T-cell response, remodeling the tumor immune microenvironment from “cold” to “hot”. This mechanism may explain its efficacy in delaying recurrence. The variable overall survival benefit suggests that HIPEC primarily serves as an immune primer, enhancing subsequent immune-checkpoint inhibitor efficacy. Consequently, HIPEC should be redefined as a strategic immune modulator. Priority must be given to studies on synergistic “HIPEC-immune-checkpoint inhibitor” sequences and predictive biomarkers to select patients most likely to benefit. Through such strategies, HIPEC can evolve into a foundational component of immunotherapy for high-risk gastric cancer.

Keywords: Gastric cancer; Hyperthermic intraperitoneal chemotherapy; Tumor immune microenvironment; Immunogenic cell death; Immune checkpoint inhibitors

Core Tip: Postoperative hyperthermic intraperitoneal chemotherapy should be reconceptualized as an immunogenic primer that activates systemic anti-tumor immunity, rather than be viewed merely as a local cytoreductive treatment. This repositions hyperthermic intraperitoneal chemotherapy as a strategic foundation for synergistic combination with immune-checkpoint inhibitors. Consequently, future research should prioritize the definition of optimal synergistic sequences and the identification of predictive biomarkers to pave the way for this precision immunotherapy strategy.