NLRC5 potentiates anti-tumor CD8+T cells responses by activating interferon-β in endometrial cancer

Objectives: NLR family CARD domain containing 5 (NLRC5) could promote major histocompatibility complex class I (MHC-I)-dependent CD8+ T cell-mediated anticancer immunity. In this study, the immunosurveillance role and underlying mechanisms of NLRC5 in endometrial cancer (EC) were characterized.Methods: CD8+ T cells were separated from healthy women's peripheral blood by using magnetic beads. The effect of NLRC5 and interferon-& beta; (IFN-& beta;) on immunosurveillance of EC were examined through a mouse tumor model and a CD8+ T cell-EC cell coculture system after NLRC5 overexpression and IFN-& beta; overexpression or depletion. The effect of NLRC5 on IFN-& beta; expression was examined with gain-and loss-of-function experiments.Results: NLRC5 overexpression in the EC cell and CD8+ T cell coculture system inhibited EC cell proliferation and migration and promoted EC cell apoptosis and CD8+ T cell proliferation. In vivo, NLRC5 overexpression increased the proportion of CD8+ T cells and inhibited EC progression. Furthermore, IFN-& beta; overexpression in the EC cell and CD8+ T cell coculture system activated CD8+ T cell proliferation; however, genetic depletion of IFN-& beta; exerted the opposite effects. In addition, NLRC5 could negatively regulate IFN-& beta; expression in EC cells. Mech-anistically, NLRC5 potentiated the antitumor responses of CD8+ T cells to EC by activating IFN-& beta;. Conclusions: Taken together, our findings demonstrated that NLRC5 potentiates anti-tumor CD8+ T cells re-sponses by activating interferon-& beta; in EC, suggesting that genetically escalated NLRC5 and IFN-& beta; may act as potential candidates for the clinical translation of adjuvant immunotherapies to patients with EC.