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

Abstract

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.

• Authors: Chufeng Chen, Jiaying Liu, Yidong Chen, Anqi Lin, Weiming Mou, Lingxuan Zhu, Tao Yang, Quan Cheng, Jian Zhang, Peng Luo
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 30 Issue 1 Pg. 1-10 (01 2023) ISSN: 1476-5500 [Electronic] England
• PMID: 35794339 (Publication Type: Journal Article, Review)
• Copyright: © 2022. The Author(s).

Chemical References

• Chromatin

Topics

• Humans
• Chromatin Immunoprecipitation Sequencing
• T-Cell Exhaustion
• High-Throughput Nucleotide Sequencing (methods)
• Chromatin (genetics)
• Neoplasms (genetics, therapy)