肿瘤细胞治疗研究
英文原题：GPR132 regulates the function of NK cells through the Gαs/CSK/ZAP70/NF-κB signaling pathway as a potential immune checkpoint.
作为质子感知GPCR受体的成员，GPR132在调节免疫细胞功能中起着至关重要的作用，但GPR132影响自然杀伤（NK）细胞的机制尚未见报道。
作为质子感应 GPCR 受体的一员，GPR132 在调节免疫细胞功能中发挥关键作用，但 GPR132 影响自然杀伤（NK）细胞的机制尚未见报道。在此，RNA-seq 显示 GPR132 在活化 NK 细胞中的表达降低，并且与 WT 小鼠相比，GPR132 -/- 小鼠中成熟 NK 细胞的比例大幅增加，具有更强的抗黑色素瘤能力。进一步研究表明，GPR132 缺陷的 NK92 细胞表达更多的 GzmB 和 IFN-，并表现出更强的细胞毒性。机制上，GPR132 通过 CSK/ZAP70/NF- B 信号轴调控 NK 细胞功能。GPR132 的下调削弱了乳酸对 NK 细胞功能的抑制，从而增强 CAR-NK 细胞针对结直肠癌的功能执行。这些结果突出了 GPR132 在 NK 细胞功能调节中此前未被认识的作用，并且抑制 GPR132 为 NK 细胞治疗提供了更新的见解。
As a member of the proton-sensing GPCR receptors, GPR132 plays a crucial role in regulating immune cell functions, but the mechanism by which GPR132 affects natural killer (NK) cells has not yet been reported. Here, RNA-seq displayed that the expression of GPR132 was reduced in activated NK cells, and the proportion of mature NK cells in GPR132 -/- 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- and exhibited stronger cytotoxicity. Mechanically, GPR132 regulates NK cell function through the CSK/ZAP70/NF- B 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.
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