Oral Cancer-derived miR-762 Suppresses T Cell Infiltration and Activation by Horizontally Inhibition of CXCR3 Expression

Oral cancer is an immune cold tumor characterized by an immunosuppressive microenvironment with low cytotoxic activity to eliminate tumor cells. Tumor escape is one of the initial steps in cancer development. Understanding the underlying mechanisms of cancer escape can help researchers develop new treatment strategies. In this study, we found that the oral oncogenic miR-762 can suppress T-cell recruitment and cytotoxic activation in the tumor microenvironment through horizontal transmission from oral cancer cells to adaptive immune T-cells. This horizontal transmission of miR-762 directly suppresses CXCR3 expression in T-cells, inhibiting CXCR3-induced T-cell migration and downstream T-cell cytotoxic activity by disrupting AKT activation. Additionally, miR-762 transmission suppressed T-cell activation marker expression, T-cell proliferation, IL-12 secretion, and T-cell cytotoxicity. In conclusion, our findings reveal a novel miR-762/CXCR3 axis that regulates the immunosuppressive microenvironment in oral cancer and may be a potential RNA-targeted therapeutic approach to restore the anti-tumor immune response in oral cancer immunotherapy.