文章：

ATAC-seq在肿瘤特异性T细胞耗竭中的应用

Application of ATAC-seq in tumor-specific T cell exhaustion 

原文发布日期：2022-07-06 

英文摘要：

Researches show that chronic viral infection and persistent antigen and/or inflammatory signal exposure in cancer causes the functional status of T cells to be altered, mainly by major changes in the epigenetic and metabolic environment, which then leads to T cell exhaustion. The discovery of the immune checkpoint pathway is an important milestone in understanding and reversing T cell exhaustion. Antibodies targeting these pathways have shown superior ability to reverse T cell exhaustion. However, there are still some limitations in immune checkpoint blocking therapy, such as the short-term nature of therapeutic effects and high individual heterogeneity. Assay for transposase-accessible chromatin with sequencing(ATAC-seq) is a method used to analyze the accessibility of whole-genome chromatin. It uses hyperactive Tn5 transposase to assess chromatin accessibility. Recently, a growing number of studies have reported that ATAC-seq can be used to characterize the dynamic changes of epigenetics in the process of T cell exhaustion. It has been determined that immune checkpoint blocking can only temporarily restore the function of exhausted T cells because of an irreversible change in the epigenetics of exhausted T cells. In this study, we review the latest developments, which provide a clearer molecular understanding of T cell exhaustion, reveal potential new therapeutic targets for persistent viral infection and cancer, and provide new insights for designing effective immunotherapy for treating cancer and chronic infection. 

摘要翻译： 

研究表明，慢性病毒感染以及癌症中持续存在的抗原和/或炎症信号暴露会导致T细胞功能状态改变，这主要源于表观遗传和代谢环境的重大变化，进而引发T细胞耗竭。免疫检查点通路的发现是理解和逆转T细胞耗竭的重要里程碑。针对这些通路的抗体已显示出卓越的逆转T细胞耗竭能力。然而免疫检查点阻断疗法仍存在局限性，例如治疗效果持续时间短及个体异质性高等问题。转座酶可及染色质测序（ATAC-seq）是一种用于分析全基因组染色质可及性的方法，其通过超活性Tn5转座酶评估染色质开放性。近期越来越多研究报道，ATAC-seq可用于表征T细胞耗竭过程中表观遗传的动态变化。研究证实，由于耗竭T细胞表观遗传的不可逆改变，免疫检查点阻断仅能暂时恢复其功能。本研究综述了最新进展，这些进展为理解T细胞耗竭提供了更清晰的分子机制认知，揭示了针对持续性病毒感染和癌症的潜在新治疗靶点，并为设计治疗癌症和慢性感染的有效免疫疗法提供了新见解。

原文链接：

Application of ATAC-seq in tumor-specific T cell exhaustion