Blocking TIGIT/CD155 Signal Reverses CD8+T Cell Exhaustion and Enhances the Anti-Tumor Ability of Cervical Cancer

Abstract Objective：TIGIT/CD155 has attracted widespread attention as a new immune checkpoint and a potential target for cancer immunotherapy. In our study, we evaluated the role of TIGIT/CD155 checkpoints in the progression of cervical cancer.Methods. Detect the expression of CD155 and TIGIT in cervical cancer tissues by flow cytometry, immunohistochemistry and gene expression profiling. In vivo and in vitro experiments have proved that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines.Methods.：Detect the expression of CD155 and TIGIT in cervical cancer tissues by flow cytometry, immunohistochemistry (IHC) and gene expression profiling. In vivo and in vitro experiments have proved that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines.Changes in NF-κB and ERK pathways detected by western blot (WB) after blocking TIGIT/CD155 signalingResults：We found that the expression of TIGIT is elevated in patients with cervical cancer. The high expression of TIGIT in CD8+T lymphocytes of cervical cancer patients promotes the failure of CD8+T lymphocytes. In addition, CD155 is highly expressed in cervical cancer tissues and negatively correlated with the infiltration level of CD8+ T cells. We showed that phosphorylated TIGIT binds to CD155 to inhibit NF-κB and ERK activation by recruiting SHIP-1, leading to down-regulation of cytokine production. Inactivated CD8+T cells, after blocking TIGIT, the inhibitory effect of SHIP-1 on CD8+T cells is weakened, and the activation of NF-κB and ERK is enhanced. In vivo and in vitro experiments have proved that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines. Injecting blocking antibody TIGIT in vivo could inhibit tumor growth and promote CD8+T lymphocyte function. Combining blocking TIGIT and PD-1 further increased the effect of the blocking antibody TIGIT. Conclusions：Our research shows that TIGIT/CD155 is a potential therapeutic target for cervical cancer.