Surgery-mediated tumor-promoting effects on the immune microenvironment

Surgical resection continues to be the mainstay treatment for solid cancers even though chemotherapy and immunotherapy have significantly improved patient overall survival and progression-free survival. Numerous studies have shown that surgery induces the dissemination of circulating tumor cells (CTCs) and that the resultant inflammatory response promotes occult tumor growth and the metastatic process by forming a supportive tumor microenvironment (TME). Surgery-induced platelet activation is one of the initial responses to a wound and the formation of fibrin clots can provide the scaffold for recruited inflammatory cells. Activated platelets can also shield CTCs to protect them from blood shear forces and promote CTCs evasion of immune destruction. Similarly, neutrophils are recruited to the fibrin clot and enhance cancer metastatic dissemination and progression by forming neutrophil extracellular traps (NETs). Activated macrophages are also recruited to surgical sites to facilitate the metastatic spread. More importantly, the body's response to surgical insult results in the recruitment and expansion of immunosuppressive cell populations (i.e. myeloid-derived suppressor cells and regulatory T cells) and in the suppression of natural killer (NK) cells that contribute to postoperative cancer recurrence and metastasis. In this review, we seek to provide an overview of the pro-tumorigenic mechanisms resulting from surgery's impact on these cells in the TME. Further understanding of these events will allow for the development of perioperative therapeutic strategies to prevent surgery-associated metastasis.