TRPV1是一种非选择性Ca2通道蛋白，广泛表达，在多种癌症的发生、发展过程中发挥重要作用。 TRPV1通道的激活可以通过调节增殖、凋亡和迁移来影响肿瘤进展。一些研究还表明，激活TRPV1可以通过调节肿瘤免疫来影响肿瘤进展。然而，TRPV1对非小细胞肺癌（NSCLC）发生发展的影响尚未明确。利用癌症基因组图谱（TCGA）数据库和10×Genomics的空间转录组数据集分析TRPV1在各种肿瘤中的表达组织。通过细胞计数试剂盒8 (CCK8)、集落形成和流式细胞术检查细胞增殖和凋亡。采用免疫组织化学、qPCR和蛋白质印迹法测定TRPV1和其他相关分子的mRNA和蛋白表达水平。 BALB/C 和 C57BL/6J 小鼠的肿瘤异种移植物用于确定 TRPV1 对 NSCLC 体内发育的影响。通过 LC-MS/MS、ELISA 和免疫组织化学检查神经递质含量。通过流式细胞术评估免疫细胞浸润。在本研究中，我们发现TRPV1表达在NSCLC中显着上调，并且TRPV1高表达的患者预后较差。 TRPV1 敲低可显着抑制 NSCLC 增殖并通过 Ca2 -IGF1R 信号传导诱导细胞凋亡。此外，TRPV1敲低导致NSCLC中CD4 T细胞、CD8 T细胞、GZMB CD8 T细胞和DC的浸润增加，并减少免疫抑制性MDSC的浸润。此外，TRPV1敲除有效降低了M2巨噬细胞标记物CD163的表达，并增加了M1相关共刺激标记物CD86的表达。 TRPV1 的敲低或敲除可通过抑制 NSCLC 中的 γ-氨基丁酸 (GABA) 分泌，显着抑制肿瘤生长并促进抗肿瘤免疫反应。我们的研究表明，TRPV1 在 NSCLC 中充当肿瘤促进剂，介导促增殖和抗凋亡作用通过 IGF1R 信号传导和调节 GABA 释放来影响肿瘤免疫反应，对 NSCLC 产生影响。© 2023。Springer Nature Switzerland AG。

TRPV1 is a nonselective Ca2+ channel protein that is widely expressed and plays an important role during the occurrence and development of many cancers. Activation of TRPV1 channels can affect tumour progression by regulating proliferation, apoptosis and migration. Some studies have also shown that activating TRPV1 can affect tumour progression by modulating tumour immunity. However, the effects of TRPV1 on the development of non-small cell lung cancer (NSCLC) have not been explored clearly.The Cancer Genome Atlas (TCGA) database and spatial transcriptomics datasets from 10 × Genomics were used to analyze TRPV1 expression in various tumour tissues. Cell proliferation and apoptosis were examined by cell counting kit 8 (CCK8), colony formation, and flow cytometry. Immunohistochemistry, qPCR, and western blotting were used to determine the mRNA and protein expression levels of TRPV1 and other related molecules. Tumour xenografts in BALB/C and C57BL/6J mice were used to determine the effects of TRPV1 on NSCLC development in vivo. Neurotransmitter content was examined by LC-MS/MS, ELISA and Immunohistochemistry. Immune cell infiltration was assessed by flow cytometry.In this study, we found that TRPV1 expression was significantly upregulated in NSCLC and that patients with high TRPV1 expression had a poor prognosis. TRPV1 knockdown can significantly inhibit NSCLC proliferation and induce cell apoptosis through Ca2+-IGF1R signaling. In addition, TRPV1 knockdown resulted in increased infiltration of CD4+ T cells, CD8+ T cells, GZMB+CD8+ T cells and DCs and decreased infiltration of immunosuppressive MDSCs in NSCLC. In addition, TRPV1 knockout effectively decreased the expression of M2 macrophage markers CD163 and increased the expression of M1-associated, costimulatory markers CD86. Knockdown or knockout of TRPV1 significantly inhibit tumour growth and promoted an antitumour immune response through supressing γ-aminobutyric acid (GABA) secretion in NSCLC.Our study suggests that TRPV1 acts as a tumour promoter in NSCLC, mediating pro-proliferative and anti-apoptotic effects on NSCLC through IGF1R signaling and regulating GABA release to affect the tumour immune response.© 2023. Springer Nature Switzerland AG.