Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Cancer Gene Ther. 2023 Jan;30(1):1-10. doi: 10.1038/s41417-022-00495-w. Epub 2022 Jul 6.
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.
研究表明，慢性病毒感染和肿瘤中持续的抗原和/或炎症信号暴露会改变 T 细胞的功能状态，主要是通过表观遗传和代谢环境的重大变化，从而导致 T 细胞衰竭。免疫检查点途径的发现是理解和逆转 T 细胞衰竭的重要里程碑。针对这些途径的抗体显示出了优越的逆转 T 细胞衰竭的能力。然而，免疫检查点阻断疗法仍然存在一些局限性，例如治疗效果的短期性和个体间的高度异质性。转座酶可及染色质的测序（ATAC-seq）是一种用于分析全基因组染色质可及性的方法。它使用高活性 Tn5 转座酶来评估染色质可及性。最近，越来越多的研究报告称，ATAC-seq 可用于描述 T 细胞衰竭过程中表观遗传学的动态变化。已经确定，由于衰竭 T 细胞的表观遗传学发生了不可逆转的变化，免疫检查点阻断只能暂时恢复衰竭 T 细胞的功能。在这项研究中，我们综述了最新的研究进展，这些进展为 T 细胞衰竭提供了更清晰的分子理解，揭示了持续性病毒感染和癌症的潜在新治疗靶点，并为设计有效的癌症和慢性感染治疗的免疫疗法提供了新的见解。
