Key Laboratory of Tumor Immunity, Center of Infection and Immunization, Department of Immunology, School of Basic Medical Sciences, Cancer Hospital Affiliated To Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.
Biotherapy Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Cancer Immunol Immunother. 2021 Jun;70(6):1649-1665. doi: 10.1007/s00262-020-02807-1. Epub 2020 Dec 10.
The aim of this study is to investigate the gene expression module of tumor-infiltrating CD4T cells and its potential roles in modulating immune cell functions in triple-negative breast cancer. Differentially expressed genes were identified by comparison of the expression profile in CD4T cells isolated from tumor tissues and peripheral blood of TNBC patients respectively. The differential expression analysis was conducted using R, and then the functional and pathway enrichment of the DEGs were analyzed using GSEA, followed by integrated regulatory network construction and genetic analysis of tumor-infiltrating immune cells based on a scientific deconvolution algorithm. As a result, abundant Treg and exhausted lymphocytes were detected, accompanied by largely decreased of effector/memory and cytotoxic T cells. Immune-related gene correlation analysis showed that the extent of follicular helper T cells gene expression signatures were inversely associated with those of CD4 naive T cells and CD4 memory resting T cells, but positively correlated with that of CD4 memory activated T cells. In addition, we found five core genes including IFNG, CTLA4, FAS, CXCR6, and JUN were significantly over expressed in CD4 TILs which may contribute to exhaustion of lymphocytes and participate in biological processes associated with regulation of chemotaxis. Study provides a comprehensive understanding of the roles of DEGs associated with the chemotactic and exhausted immunophenotypes of CD4 TILs that are a valuable resource from which future investigation may be carried out to better understand the mechanisms that promote TNBC progression.
本研究旨在探讨肿瘤浸润性 CD4T 细胞的基因表达模块及其在调节三阴性乳腺癌免疫细胞功能中的潜在作用。通过比较分别从肿瘤组织和三阴性乳腺癌患者外周血中分离的 CD4T 细胞的表达谱，鉴定差异表达基因。使用 R 进行差异表达分析，然后使用 GSEA 分析 DEGs 的功能和途径富集，接着基于科学的去卷积算法构建肿瘤浸润免疫细胞的综合调控网络和遗传分析。结果表明，大量 Treg 和耗竭淋巴细胞被检测到，同时效应/记忆和细胞毒性 T 细胞大量减少。免疫相关基因相关性分析表明，滤泡辅助 T 细胞基因表达特征的程度与 CD4 幼稚 T 细胞和 CD4 记忆静止 T 细胞的程度呈负相关，但与 CD4 记忆激活 T 细胞的程度呈正相关。此外，我们发现了五个核心基因，包括 IFNG、CTLA4、FAS、CXCR6 和 JUN，在 CD4TIL 中显著过表达，这可能导致淋巴细胞耗竭，并参与与趋化调节相关的生物学过程。该研究为深入了解与 CD4TIL 趋化和耗竭免疫表型相关的 DEGs 的作用提供了全面的认识，为进一步研究促进三阴性乳腺癌进展的机制提供了有价值的资源。
