Tumor Necrosis Factor Alpha: Implications of Anesthesia on Cancers

SIMPLE SUMMARY: Cancer ranks as a leading cause of death worldwide, which is often the result of recurrence and metastasis. Surgical resection is the mainstay of cancer treatment for potentially removable solid tumors. However, surgery-induced stress responses may lead to immunosuppression and subsequent cancer regrowth and spread. Evidence shows that the tumor microenvironment plays an essential role in disease progression through mechanisms such as inflammation promotion. Tumor necrosis factor alpha (TNF-α) is one of the pro-inflammatory cytokines found in cancer patients and is reported to be involved in the immune system as well as in the surveillance of tumor growth. To date, several studies have demonstrated that various anesthetic agents or techniques and perioperative management have varying effects on innate and cellular immunity, the enhancement of adrenergic-inflammatory responses, and the activation of cancer-promoting cellular signaling pathways, which may be associated with long-term cancer outcomes. This review outlines the current knowledge of anesthesia implications on TNF-α release and provides potential anesthetic strategies for improving patient survival. ABSTRACT: Cancer remains a major public health issue and a leading cause of death worldwide. Despite advancements in chemotherapy, radiation therapy, and immunotherapy, surgery is the mainstay of cancer treatment for solid tumors. However, tumor cells are known to disseminate into the vascular and lymphatic systems during surgical manipulation. Additionally, surgery-induced stress responses can produce an immunosuppressive environment that is favorable for cancer relapse. Up to 90% of cancer-related deaths are the result of metastatic disease after surgical resection. Emerging evidence shows that the interactions between tumor cells and the tumor microenvironment (TME) not only play decisive roles in tumor initiation, progression, and metastasis but also have profound effects on therapeutic efficacy. Tumor necrosis factor alpha (TNF-α), a pleiotropic cytokine contributing to both physiological and pathological processes, is one of the main mediators of inflammation-associated carcinogenesis in the TME. Because TNF-α signaling may modulate the course of cancer, it can be therapeutically targeted to ameliorate clinical outcomes. As the incidence of cancer continues to grow, approximately 80% of cancer patients require anesthesia during cancer care for diagnostic, therapeutic, or palliative procedures, and over 60% of cancer patients receive anesthesia for primary surgical resection. Numerous studies have demonstrated that perioperative management, including surgical manipulation, anesthetics/analgesics, and other supportive care, may alter the TME and cancer progression by affecting inflammatory or immune responses during cancer surgery, but the literature about the impact of anesthesia on the TNF-α production and cancer progression is limited. Therefore, this review summarizes the current knowledge of the implications of anesthesia on cancers from the insights of TNF-α release and provides future anesthetic strategies for improving oncological survival.