Redefining surgical oncology: active immune microenvironment modulation beyond tumor resection

Surgical resection remains central to curative treatment for many solid tumors, yet it also triggers rapid and clinically relevant remodeling of the tumor immune microenvironment (TME). Perioperative stress can transiently blunt antitumor immunity, amplify inflammatory signaling, and create conditions that favor residual disease persistence and metastatic outgrowth. This review summarizes mechanistic and translational evidence from PubMed and Web of Science (through October 2025) to define how surgical injury and systemic stress responses reshape immune and stromal compartments across tumor types. We highlight key perioperative vulnerabilities and actionable entry points, including intraoperative approaches (localized drug delivery, myeloid and lymphoid reprogramming, intraoperative radiotherapy, and oncolytic strategies) and systemic measures (anesthetic technique, β-adrenergic blockade, COX-2 inhibition, and corticosteroid use). We also discuss how neoadjuvant and adjuvant immunotherapies may complement surgery by preserving perioperative immune competence and promoting durable immune surveillance. Finally, we outline priorities for biomarker-driven trials that align intervention timing with tumor-specific biology and incorporate high-resolution immune profiling and monitoring. Overall, the evidence supports viewing surgery not only as tumor removal but also as a modifiable immunologic window that can be leveraged to reduce recurrence risk and improve long-term outcomes.