CD226 识别肿瘤微环境中的功能性 CD8+T 细胞并预测人类胃癌的更好结果,Frontiers in Immunology

当前位置： X-MOL 学术 › Front. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CD226 识别肿瘤微环境中的功能性 CD8+T 细胞并预测人类胃癌的更好结果
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2023-03-28 , DOI: 10.3389/fimmu.2023.1150803
Hao Huang _{1,

2,

3} , Ziyi Huang _{4,

5,

6} , Junwei Ge _{1,

2,

3} , Jiayi Yang _{1,

2,

3} , Junjun Chen _{1,

2,

3} , Bin Xu _{1,

2,

3} , Shaoxian Wu _{1,

2,

3} , Xiao Zheng _{1,

2,

3} , Lujun Chen _{1,

2,

3} , Xueguang Zhang _{4,

5,

6} , Jingting Jiang _{1,

2,

3}

Affiliation

众所周知，CD226 是淋巴细胞和单核细胞等多种免疫细胞的关键激活受体，可在肿瘤微环境 (TME) 中促进抗肿瘤免疫。在此，我们展示了 CD226 在 CD8 中的关键调节作用+人胃癌 (GC) TME 中 T 细胞介导的抗肿瘤反应。具体而言，癌组织中 CD226 表达的增加与 GC 患者更好的临床结果显着相关。此外，增加的浸润性 CD226+CD8+T细胞和浸润性CD226比例增加+CD8+CD8中的T细胞+癌组织内的 T 亚群也可能是 GC 患者有价值的预后预测因子。从机械上讲，使用测序 (ATAC-seq) 分析的转座酶可及染色质测定表明染色质可及性CD226CD4+和CD8+TILs明显高于CD8+正常组织中的 T 细胞。进一步分析表明，CD8+TILs高表达免疫检查点分子，如泰吉特,滞后3，和HAVCR2, 这意味着 CD8+TIL 更加疲惫。此外，我们的多色免疫组织化学染色 (mIHC) 显示，GC 患者的 IFN-γ 频率较高+CD226+CD8+TIL 预后较差。结合单细胞转录组测序（scRNA-seq）数据分析，我们发现CD8中IFN-γ和TIGIT的表达+TIL 显着正相关。TIGIT在IFN-γ中的表达+CD226+CD8+TIL 更高，而在 IFN-γ 中-CD226+CD8+TIL 显着降低。相关性分析表明，CD226与效应 T 细胞的评分呈正相关，但与 Treg 和肿瘤相关巨噬细胞 (TAM) 等免疫抑制因子的评分呈负相关。总的来说，我们发现 CD226 的频率+CD8+TILs 是 GC 患者极好的预后预测因子。我们的研究结果提供了对共刺激受体 CD226 与肿瘤细胞以及 GC 中 TME 中浸润性免疫细胞之间相互作用模式的见解。

"点击查看英文标题和摘要"

CD226 identifies functional CD8+T cells in the tumor microenvironment and predicts a better outcome for human gastric cancer

It is well-known that CD226 serves as a critical activating receptor on various immune cells, such as lymphocytes and monocytes, and it is suggested to promote anti-tumor immunity in the tumor microenvironment (TME). Herein, we showed a crucial regulatory role of CD226 in CD8+T cell-mediated anti-tumor response in TME of human gastric cancer (GC). Specifically, the increased CD226 expression in cancer tissues was significantly associated with better clinical outcomes in GC patients. Moreover, the increased infiltrating CD226+CD8+T cells and the increased ratio of infiltrating CD226+CD8+T cells in CD8+T subpopulation within cancer tissues could also be valuable prognostic predictors for GC patients. Mechanically, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis revealed that the chromatin accessibility of CD226 in CD4+ and CD8+TILs was significantly higher than that in CD8+T cells in normal tissues. Further analysis showed that CD8+TILs highly expressed immune checkpoint molecules, such as TIGIT, LAG3, and HAVCR2, which means CD8+TILs are more exhausted. In addition, our multi-color immunohistochemical staining (mIHC) revealed that GC patients with higher frequency of IFN-γ+CD226+CD8+TILs showed poorer prognosis. Combined with the single-cell transcriptome sequencing (scRNA-seq) data analysis, we found that the expressions of IFN-γ and TIGIT in CD8+TILs were significantly and positively correlated. The expression of TIGIT in IFN-γ+CD226+CD8+TILs was higher, while that in IFN-γ-CD226+CD8+TILs was significantly lower. The correlation analysis showed that the expression of CD226 was positively correlated with the score of effector T cells but negatively correlated with that of immunosuppressive factors, such as Tregs and tumor-associated macrophages (TAMs). Collectively, we showed that the frequency of CD226+CD8+TILs was an excellent prognostic predictor for GC patients. Our findings provided insights into the interaction pattern between co-stimulatory receptor CD226 and tumor cells as well as the infiltrating immune cells in the TME in GC.

更新日期：2023-03-28

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南