期刊论文详细信息
Frontiers in Pharmacology
A systematic and comprehensive analysis of T cell exhaustion related to therapy in lung adenocarcinoma tumor microenvironment
Pharmacology
Peipei Hu1  Jinjian Chen1  Jiahao Ma2 
[1] Department of General Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;Department of General Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;Key Laboratory of Nano-carbon Modified Film Technology of Henan Province, Diagnostic Laboratory of Animal Diseases, School of Pharmacy, Xinxiang University, Xinxiang, China;
关键词: T exhausted;    lung adenocarcinoma;    single cell sequencing;    biomarkers;    tumor microenvironment;   
DOI  :  10.3389/fphar.2023.1126916
 received in 2022-12-18, accepted in 2023-01-23,  发布年份 2023
来源: Frontiers
PDF
【 摘 要 】

Background: T cell exhaustion (TEX) is an important immune escape mechanism, and an in-depth understanding of it can help improve cancer immunotherapy. However, the prognostic role of TEX in malignant lung adenocarcinoma (LUAD) remains unclear.Methods: Through TCGA and GEO datasets, we enrolled a total of 498 LUAD patients. The patients in TCGA-LUAD were unsupervised clustered into four clusters according to TEX signaling pathway. WGCNA analysis, survival random forest analysis and lasso regression analysis were used to select five differentially expressed genes among different clusters to construct a TEX risk model. The risk model was subsequently validated with GEO31210. By analyzing signaling pathways, immune cells and immune checkpoints using GSEA, GSVA and Cibersortx, the relationship between TEX risk score and these variables was evaluated. In addition, we further analyzed the expression of CCL20 at the level of single-cell RNA-seq and verified it in cell experiments.Results: According to TEX signaling pathway, people with better prognosis can be distinguished. The risk model constructed by CD109, CCL20, DKK1, TNS4, and TRIM29 genes could further accurately identify the population with poor prognosis. Subsequently, it was found that dendritic cells, CD44 and risk score were closely related. The final single-cell sequencing suggested that CCL2O is a potential therapeutic target of TEX, and the interaction between TEX and CD8 + T is closely related.Conclusion: The classification of T cell depletion plays a crucial role in the clinical decision-making of lung adenocarcinoma and needs to be further deepened.

【 授权许可】

Unknown   
Copyright © 2023 Hu, Ma and Chen.

【 预 览 】
附件列表
Files Size Format View
RO202310102520153ZK.pdf 6063KB PDF download
  文献评价指标  
  下载次数:0次 浏览次数:0次