Perioperative stress–inflammation–immunosuppression axis and tumor progression: mechanistic integration and anesthetic management strategies

Abstract

Abstract Perioperative stress is an unavoidable part of surgery and may be particularly relevant in patients with cancer. Surgical trauma activates two major stress pathways, the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS), leading to surges in stress hormones, inflammatory mediators, and a temporary reduction in anti-tumor immune function. This sequence can be described as a stress–inflammation–immunosuppression axis. Experimental studies suggest that excessive activation of this axis may support postoperative survival and spread of residual tumor cells, yet clinical outcome data remain inconsistent and often depend on cancer type, stage, and the overall perioperative care bundle. This review integrates mechanistic evidence on how perioperative stress and inflammation reshape immune surveillance, including effects on natural killer (NK) cells, cytotoxic T lymphocytes, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and neutrophil extracellular traps (NETs). We also summarize how commonly used anesthetic drugs and techniques may modify stress signaling, inflammation, and immune function, and we critically appraise the current clinical evidence linking anesthetic management to biomarkers and oncologic outcomes. Finally, we propose an executable framework for individualized anesthetic planning that focuses on reducing stress peaks, limiting avoidable physiologic instability, supporting early recovery, and shortening the postoperative window of immunosuppression within enhanced recovery pathways.