Surgical trauma‐induced immunosuppression in cancer: Recent advances and the potential therapies

Abstract

Surgical resection remains the mainstay treatment for solid cancers, especially for localized disease. However, the postoperative immunosuppression provides a window for cancer cell proliferation and awakening dormant cancer cells, leading to rapid recurrences or metastases. This immunosuppressive status after surgery is associated with the severity of surgical trauma since immunosuppression induced by minimally invasive surgery is less than that of an extensive open surgery. The systemic response to tissue damages caused by surgical operations and the subsequent wound healing induced a cascade alteration in cellular immunity. After surgery, patients have a high level of circulating damage‐associated molecular patterns (DAMPs), triggering a local and systemic inflammation. The inflammatory metrics in the immediate postoperative period was associated with the prognosis of cancer patients. Neutrophils provide the first response to surgical trauma, and the production of neutrophil extracellular traps (NETs) promotes cancer progression. Activated macrophage during wound healing presents a tumor‐associated phenotype that cancers can exploit for their survival advantage. In addition, the amplification and activation of myeloid‐derived suppressor cells (MDSCs), regulatory T cells (Tregs) or the elevated programmed death ligand‐1 and vascular endothelial growth factor expression under surgical trauma, exacerbate the immunosuppression and favor of the formation of the premetastatic niche. Therapeutic strategies to reduce the cellular immunity impairment after surgery include anti‐DAMPs, anti‐postoperative inflammation or inflammatory/pyroptosis signal, combined immunotherapy with surgery, antiangiogenesis and targeted therapies for neutrophils, macrophages, MDSCs, and Tregs. Further, the application of enhanced recovery after surgery also has a feasible outcome for postoperative immunity restoration. Overall, current therapies to improve the cellular immunity under the special condition after surgery are relatively lacking. Further understanding the underlying mechanisms of surgical trauma‐related immunity dysfunction, phenotyping the immunosuppressive cells, and developing the related therapeutic intervention should be explored.

A mouse model of neoadjuvant chemotherapy followed by interval cytoreductive surgery indicates impaired efficacy of perioperative cisplatin

“…Moreover, the increase in tumor burden was prevented when delaying cisplatin treatment by 7 days. Importantly, surgical wounding induces a cascade of cytokines and growth factors, many of which overlap with cellular processes related to cancer cell growth and metastasis, including angiogenesis (39). Our observation of improved control of ascites in animals who undergo wounding compared to control animals suggests there may a relationship to those growth factors recruited for wound healing and the membrane stabilization of neovascularization within residual tumor deposits following sub-optimal cytoreduction in our model.…”

Breast Cancer and Anaesthesia: Genetic Influence

“…Tumor cells can interact direct or indirectly with neutrophils to induce NET production. Intra-and inter-cellular molecular communications generate micro-environments that act as a premetastatic niche to recruit primary tumor cells and form multiple metastases [ 144 , 145 ]. Park et al, described the relationship between metastatic cancer and NET formation through the use of anti-G-CSF blocking antibodies, which reduce the ability of 4T1 cells to induce NETosis [ 146 ].…”

Breast Cancer and Anaesthesia: Genetic Influence

“…Tumor cells can interact direct or indirectly with neutrophils to induce NET production. Intra-and inter-cellular molecular communications generate micro-environments that act as a premetastatic niche to recruit primary tumor cells and form multiple metastases (132,133).…”