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利用免疫检查点抑制剂进行免疫治疗的 Treg 迁移及其协同作用相关枢纽基因的生物信息学研究

A Bioinformatics Investigation of Hub Genes Involved in Treg Migration and Its Synergistic Effects, Using Immune Checkpoint Inhibitors for Immunotherapies.

机构信息

Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.

College of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Aug 28;25(17):9341. doi: 10.3390/ijms25179341.

Abstract

This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies.

摘要

本研究旨在鉴定参与调节性 T 细胞 (Treg) 功能和迁移的枢纽基因,为癌症免疫治疗提供潜在的治疗靶点。我们使用 GEO 数据库中的三个基因表达微阵列数据集进行了全面的生物信息学分析。通过差异表达基因 (DEG) 分析进行通路富集分析,以探讨其功能作用和潜在通路。构建蛋白质-蛋白质相互作用网络以鉴定对 Treg 活性至关重要的枢纽基因。我们进一步评估了这些枢纽基因与免疫检查点蛋白 (PD-1、PD-L1、CTLA4) 的共表达,并评估了它们的预后意义。通过这项综合分析,我们确定了 CCR8 是 Treg 迁移的关键参与者,并探讨了其与 ICI 联合治疗的潜在协同作用。我们的研究结果表明,CCR8 靶向治疗可能增强癌症免疫治疗效果,乳腺癌浸润性癌 (BRCA) 是联合治疗的一个有希望的适应证。本研究强调了 CCR8 作为生物标志物和治疗靶点的潜力,为靶向癌症治疗策略的发展做出了贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33bd/11395080/26af154f28d5/ijms-25-09341-g001.jpg

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