In summary, our results demonstrated that GPR116 receptor negatively regulated the activation and function of NK cells through Gαq/HIF1α/NF-κB signaling pathway, and knockdown of the expression of GPR116 receptor could activate NKG2D-CAR-NK92 cells by increasing the release of INF-γ and GzmB and effectively enhance their anti-pancreatic cancer effects (Fig. 7). Here, GNAQ is linked to familial pancreatic carcinoma.