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

作者：Chen, Chufeng; Liu, Jiaying; Chen, Yidong; Lin, Anqi; Mou, Weiming; Zhu, Lingxuan; Yang, Tao; Cheng, Quan; Zhang, Jian^*; Luo, Peng^*

来源：Cancer Gene Therapy, 2023, 30(1): 1-10.

DOI：10.1038/s41417-022-00495-w

• INHIBITORY RECEPTOR PD-1
• CHROMATIN ACCESSIBILITY
• EPIGENETIC LANDSCAPE
• WIDESPREAD INCREASE
• MEMORY
• EFFECTOR
• REVEALS
• BATF
• DYSFUNCTION
• RESPONSES

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.

• 单位
  南方医科大学