Fig. 1

Mechanisms of postoperative immunosuppression. Surgical debulking initiates inflammatory, neuroendocrine and metabolic events, which result in altered cytokine levels (decrease in IL-2, IL-12 and IFN-γ; increase in IL-6/8, IL-10 and TNF-α) and release of growth factors (VEGF - green oval, PDGF - blue oval, TGF-β - pink oval), clotting factors, and stress hormones (catecholamines - yellow circle, prostaglandins - purple circle). While essential for wound healing and pain management, these events lead to the expansion of Tregs, MDSC, and M2 macrophages. Increase in these regulatory immune cells leads to augmented expression of PD-1/CTLA-4, decreased T-cell proliferation, and impaired NK-cell cytotoxicity, resulting in an overall state of immunosuppression. In conjunctions with surgical trauma, other postoperative factors, including sepsis, blood loss, hypothermia, anesthetics, analgesics and anastomotic complications contribute to immunosuppression. Abbreviations: VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; TGF-β; Transforming growth factor beta; Tregs, regulatory T cells; MDSC, myeloid derived suppressor cells; PD-1, programmed cell death protein 1; CTLA-4, cytotoxic T lymphocyte associated protein 4