国内团队:表观遗传如何调控肿瘤浸润T淋巴细胞
创作:Lexi 审核:Lexi 01月13日
  • 比较结直肠癌(CRC)患者的肿瘤反应性和旁观者CD8+ T细胞转录组和甲基化组特征;
  • 鉴定出一种独特的肿瘤反应性CD8+ T细胞的甲基化模式,其肿瘤反应性标志物CD39和CD103被特异性去甲基化;
  • naïveT细胞向肿瘤反应性CD8+ T细胞转化过程经历甲基化动态变化,导致每个CD8+ T细胞亚型的表达程序不同;
  • 包括三个耗竭相关基因(NR4A1、BATF和EGR2)在内的若干转录因子在肿瘤反应性CD8+ T细胞中具有潜在调控作用。
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Lexi
肿瘤反应性CD8+肿瘤浸润淋巴细胞(TILs)是一种能够特异性识别和破坏肿瘤的T细胞亚型。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甲基化状态尚未被阐明。来自北京大学的张泽民、任仙文以及北京世纪坛医院的彭吉润研究团队近日在Genome Biology发表最新研究,支持DNA甲基化参与肿瘤反应性和旁观者CD8+ TILs的形成,并为开发新的DNA甲基化标志物和未来的治疗提供了宝贵资源。
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Genome Biology [IF:14.028]

Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis

全基因组DNA甲基化分析显示大肠癌患者肿瘤反应性CD8+ T细胞具有明显的表观遗传学特征

10.1186/s13059-019-1921-y

2019-12-31, Article

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Background: 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.
Results: 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.
Conclusion: 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.

First Authors:
Rui Yang,Sijin Cheng,Nan Luo

Correspondence Authors:
Jirun Peng,Xianwen Ren,Zemin Zhang

All Authors:
Rui Yang,Sijin Cheng,Nan Luo,Ranran Gao,Kezhuo Yu,Boxi Kang,Li Wang,Qiming Zhang,Qiao Fang,Lei Zhang,Chen Li,Aibin He,Xueda Hu,Jirun Peng,Xianwen Ren,Zemin Zhang

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