Interleukin-6 (IL-6)-associated tumor microenvironment remodelling and cancer immunotherapy

Interleukin-6 (IL-6) is a pro-inflammatory cytokine playing a pivotal role during inflammation and immune responses. In the recent years, the function of IL-6 in the tumor microenvironment (TME) for affecting tumorigenesis and immunotherapy response has been investigated. The genetic mutations are mainly responsible for the development of cancer, while interactions in TME are also important, involving both cancers and non-cancerous cells. IL-6 plays a significant role in these interactions, enhancing the proliferation, survival and metastasis of tumor cells through inflammatory pathways, highlighting its carcinogenic function. Multiple immune cells including macrophages, T cells , myeloid-derived suppressor cells, dendritic cells and natural killer cells can be affected by IL-6 to develop immunosuppressive TME. IL-6 can also participate in the immune evasion through increasing levels of PD-L1, compromising the efficacy of therapeutics. Notably, IL-6 exerts a double-edge sword function and it can dually increase or decrease cancer immunotherapy , providing a challenge for targeting this cytokine in cancer therapy. Highlighting the complicated function of IL-6 in TME can lead to the development of effective therapeutics for cancer immunity . • IL-6 is an inflammatory cytokine regulating tumorigenesis and immune responses. • IL-6 acts as a double-edged sword and dually increases/decreases cancer immunotherapy . • IL-6 affects the immune cells and other factors in TME to create immunosuppressive condition. • Targeting IL-6 is of importance in cancer immunotherapy and reversing immune evasion.