当前位置: X-MOL 学术Genome Biol. › 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.)
Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis
Genome Biology ( IF 10.1 ) Pub Date : 2019-12-31 , DOI: 10.1186/s13059-019-1921-y
Rui Yang 1 , Sijin Cheng 1 , Nan Luo 2, 3 , Ranran Gao 1 , Kezhuo Yu 4 , Boxi Kang 1 , Li Wang 1 , Qiming Zhang 1 , Qiao Fang 4 , Lei Zhang 4 , Chen Li 5 , Aibin He 5 , Xueda Hu 1 , Jirun Peng 2, 3 , Xianwen Ren 1 , Zemin Zhang 1, 4
Affiliation  

Tumor-reactive CD8+ tumor-infiltrating lymphocytes (TILs) represent a subtype of T cells that can recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells has important therapeutic implications. Yet the DNA methylation status of this T cell subtype has not been elucidated. In this study, we segregate tumor-reactive and bystander CD8+ TILs, as well as naïve and effector memory CD8+ T cell subtypes as controls from colorectal cancer patients, to compare their transcriptome and methylome characteristics. Transcriptome profiling confirms previous conclusions that tumor-reactive TILs have an exhausted tissue-resident memory signature. Whole-genome methylation profiling identifies a distinct methylome pattern of tumor-reactive CD8+ T cells, with tumor-reactive markers CD39 and CD103 being specifically demethylated. In addition, dynamic changes are observed during the transition of naïve T cells into tumor-reactive CD8+ T cells. Transcription factor binding motif enrichment analysis identifies several immune-related transcription factors, including three exhaustion-related genes (NR4A1, BATF, and EGR2) and VDR, which potentially play an important regulatory role in tumor-reactive CD8+ T cells. Our study supports the involvement of DNA methylation in shaping tumor-reactive and bystander CD8+ TILs, and provides a valuable resource for the development of novel DNA methylation markers and future therapeutics.

中文翻译:

全基因组 DNA 甲基化分析揭示结直肠癌患者肿瘤反应性 CD8+ T 细胞的独特表观遗传特征

肿瘤反应性CD8+肿瘤浸润淋巴细胞(TIL)代表T细胞的一种亚型,可以特异性识别和破坏肿瘤。了解肿瘤反应性 CD8+ T 细胞的调节机制具有重要的治疗意义。然而,这种 T 细胞亚型的 DNA 甲基化状态尚未阐明。在这项研究中,我们从结直肠癌患者中分离出肿瘤反应性和旁观者 CD8+ TIL,以及幼稚和效应记忆 CD8+ T 细胞亚型作为对照,以比较其转录组和甲基化组特征。转录组分析证实了之前的结论,即肿瘤反应性 TIL 具有耗尽的组织驻留记忆特征。全基因组甲基化分析可识别肿瘤反应性 CD8+ T 细胞的独特甲基化模式,其中肿瘤反应性标记物 CD39 和 CD103 被特异性去甲基化。此外,在幼稚 T 细胞转变为肿瘤反应性 CD8+ T 细胞的过程中观察到动态变化。转录因子结合基序富集分析鉴定了几种免疫相关转录因子,包括三个耗竭相关基因(NR4A1、BATF 和 EGR2)和 VDR,它们可能在肿瘤反应性 CD8+ T 细胞中发挥重要的调节作用。我们的研究支持 DNA 甲基化参与形成肿瘤反应性和旁观者 CD8+ TIL,并为开发新型 DNA 甲基化标记物和未来治疗方法提供了宝贵的资源。
更新日期:2019-12-31
down
wechat
bug