TIGIT promotes CD8⁺T cells exhaustion and predicts poor prognosis of colorectal cancer

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8⁺T cells. The role of TIGIT in colorectal cancer and its expression pattern in colorectal cancer infiltrating lymphocytes are still controversial. This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGIT⁺CD8⁺T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGIT⁺CD8⁺T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN-γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGIT⁺CD8⁺T cells. TGF-β1 could promote the expression of TIGIT and inhibit CD8⁺T cell function in vitro. Moreover, the accumulation of TIGIT⁺T cells in tumors was associated with advanced disease, predicted early recurrence, and reduced survival rates in colorectal cancer patients. Our results indicate that TIGIT can be a biological marker for the prognosis of colorectal cancer, and TIGIT can be used as a potential target for treatment.