瞬时受体电位香草酸受体2 (TRPV2) 是瞬时受体电位超家族的非特异性阳离子通道成员，具有多样功能。本文研究了TRPV2对胃癌 (GC) 细胞中程序性细胞死亡配体-1 (PD-L1) 的表达及其与程序性细胞死亡受体-1 (PD-1) 的结合能力的影响。使用TRPV2 小干扰 RNA 对人类 GC 细胞系进行了敲降实验，并通过流式细胞术分析表面 PD-L1 的表达及其与 PD-1 的结合能力。对 80 例原发性组织样本进行免疫组化 (IHC) 检测，并分析了 IHC 结果、临床病理因素和患者预后之间的关系。此外，还研究了 TRPV2 对胞内离子环境作用的分子机制。结果显示，TRPV2 敲降降低了 NUGC4 和 MKN7 细胞中 PD-L1 的表达水平，从而抑制了其与 PD-1 的结合。生存分析显示，TRPV2 高表达组和 PD-L1 阳性组的 5 年总生存率显著降低。在 GC 患者的 IHC 多元分析中，高 TRPV2 表达被识别为独立的预后因子。此外，TRPV2 的表达与 PD-L1 的表达呈正相关。免疫荧光分析显示，TRPV2 敲降降低了细胞内钙离子浓度 ([Ca2+]i)。与增加 [Ca2+]i 的 ionomycin/PMA (丙酸 12-肉毒碱 13 -乙酸丙酯) 处理相比，TRPV2 敲降会升高 PD-L1 的蛋白表达并促进其与 PD-1 的结合。这些结果表明，TRPV2 通过 [Ca2+]i 调节 GC 中 PD-L1 的表达及其与 PD-1 的结合能力，提示 TRPV2 在作为 GC 的免疫检查点阻断的生物标志物和治疗靶点方面的潜力。 ©2023. Society of Surgical Oncology.

Transient receptor potential vanilloid 2 (TRPV2) is a member of the TRP superfamily of non-specific cation channels with functionally diverse roles. We herein investigated the effects of TRPV2 on the expression of programmed cell death-ligand 1 (PD-L1) and its binding ability to programmed cell death-1 (PD-1) in gastric cancer (GC).Knockdown (KD) experiments were performed on human GC cell lines using TRPV2 small-interfering RNA. The surface expression of PD-L1 and its binding ability to PD-1 were analyzed by flow cytometry. Eighty primary tissue samples were assessed by immunohistochemistry (IHC), and the relationships between IHC results, clinicopathological factors, and patient prognosis were analyzed. The molecular mechanisms underlying the effects of TRPV2 on the intracellular ion environment were also investigated.TRPV2-KD decreased the expression level of PD-L1 in NUGC4 and MKN7 cells, thereby inhibiting its binding to PD-1. A survival analysis revealed that 5-year overall survival rates were significantly lower in the TRPV2 high expression and PD-L1-positive groups. In IHC multivariate analysis of GC patients, high TRPV2 expression was identified as an independent prognostic factor. Furthermore, a positive correlation was observed between the expression of TRPV2 and PD-L1. An immunofluorescence analysis showed that TRPV2-KD decreased the intracellular concentration of calcium ([Ca2+]i). Treatment with ionomycin/PMA (phorbol 12-myristate 13-acetate), which increased [Ca2+]i, upregulated the protein expression of PD-L1 and promoted its binding to PD-1.The surface expression of PD-L1 and its binding ability to PD-1 in GC were regulated by TRPV2 through [Ca2+]i, indicating the potential of TRPV2 as a biomarker and target of immune checkpoint blockage for GC.© 2023. Society of Surgical Oncology.