GPR132 regulates the function of NK cells through the Gαs/CSK/ZAP70/NF-κB signaling pathway as a potential immune checkpoint

mice was substantially increased compared to WT mice, with stronger anti-melanoma capabilities. Further investigation indicates that GPR132-deficient NK92 cells expressed more GzmB and IFN-γ and exhibited stronger cytotoxicity. Mechanically, GPR132 regulates NK cell function through the CSK/ZAP70/NF-κB signaling axis. Down-regulation of GPR132 weakens the inhibition of NK cell function by lactate, thereby enhancing the functional execution of CAR-NK cells against colorectal cancer. These results highlight the previously unrecognized role of GPR132 in the regulation of NK cell function and that inhibition of GPR132 provided an updated insight for NK cell therapy.