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

C Chen, J Liu, Y Chen, A Lin, W Mou, L Zhu… - Cancer Gene …, 2023 - nature.com
C Chen, J Liu, Y Chen, A Lin, W Mou, L Zhu, T Yang, Q Cheng, J Zhang, P Luo
Cancer Gene Therapy, 2023nature.com
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 …
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.
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