38 discovered that ICOS expression is inversely associated with the TNM stage and progression of colorectal cancer (CRC), suggesting that low ICOS expression might be a predictor of progression in patients. The elevated ICOS can induce its own anti-tumor response, not only by regulating the homeostasis of immune cells, but also by regulating the production of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and IFN-γ, which contribute to T cell immune function 29. Here, TNF is linked to neoplasm.