免疫逃逸是胃腺癌（STAD）免疫治疗失败的主要原因。本研究试图揭示FGL1影响STAD的潜在机制。通过生物信息学分析FGL1的表达、FGL1影响的信号通路以及FGL1与免疫细胞浸润的关系。采用实时定量PCR（qRT-PCR）、细胞计数试剂盒8测定、集落形成测定、流式细胞术和Transwell测定分别分析FGL1表达、细胞活力、细胞增殖、细胞凋亡和细胞侵袭。采用酶联免疫吸附法、乳酸脱氢酶法、qRT-PCR 和 Western blot 分别揭示 STAD 细胞和 CD8 T 细胞共培养后促炎细胞因子的表达、细胞毒性以及 Notch 信号相关基因的 mRNA 和蛋白表达。细胞。进行裸鼠实验验证上述结果。 FGL1在STAD中高表达，可激活Notch信号通路，且与CD8 T细胞浸润呈负相关。细胞实验证实FGL1的高表达有利于STAD细胞的增殖并阻碍其凋亡。在 STAD 和 CD8 T 细胞共培养系统中，FGL1 的敲低可促进促炎因子的表达和 CD8 T 细胞的细胞毒性。敲低FGL1可以抑制Notch信号通路相关基因的表达，Notch抑制剂的添加证明FGL1通过Notch信号通路促进免疫逃逸。本研究探讨FGL1对STAD免疫逃逸的影响，证明FGL1通过激活Notch信号通路抑制CD8 T细胞活化，从而促进STAD肿瘤免疫逃逸，为STAD患者的免疫治疗提供新的潜在诊断标志物和治疗靶点.© 2023。作者获得 Springer Science Business Media, LLC（Springer Nature 的一部分）的独家许可。

Immune escape is the major reason for immunotherapy failure in stomach adenocarcinoma (STAD). We tried to reveal the underlying mechanism of FGL1 influencing STAD in this study. Bioinformatics analyses were conducted to analyze the expression of FGL1, the signaling pathways affected by FGL1, and the relation between FGL1 and immune cell infiltration. Quantitative real-time PCR (qRT-PCR), cell counting kit-8 assay, colony formation assay, flow cytometry and Transwell assay were adopted to analyze FGL1 expression, cell viability, cell proliferation, cell apoptosis, and cell invasion, respectively. Enzyme-linked immunosorbent assay, lactate dehydrogenase method, qRT-PCR and Western blot were adopted to reveal proinflammatory cytokine expression, cytotoxicity and mRNA and protein expression of the Notch signaling-related genes, respectively, after co-culture of STAD cells and CD8+T cells. Nude mice experiment was conducted to validate the results obtained above. FGL1 expressed highly in STAD and could activate the Notch signaling pathway, and it was negatively correlated with CD8+T cell infiltration. Cell experiments confirmed that high expression of FGL1 facilitated proliferation and hindered apoptosis of STAD cells. Knockdown of FGL1 could facilitate expression of pro-inflammatory factors and the cytotoxicity of CD8+T cells in co-culture system of STAD and CD8+ T cells. Knockdown of FGL1 could suppress the expression of the Notch signaling pathway-related genes, and the addition of Notch inhibitor proved that FGL1 promoted immune escape via the Notch signaling pathway. This study investigated the influence of FGL1 on STAD immune escape and demonstrated that FGL1 inhibited CD8+ T cell activation by activating the Notch signaling pathway and thus promoted tumor immune escape in STAD, providing a new potential diagnostic marker and therapeutic target for the immunotherapy of STAD patients.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.