Application of ATAC-seq in tumor-specific T cell exhaustion
Chufeng Chen,Jiaying Liu,Yidong Chen,Anqi Lin,WeiMing Mou,Lingxuan Zhu,Tao Yang,Quan Cheng,Jian Zhang,Peng Luo +9 more
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TLDR
In this paper , the authors reviewed 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.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. read more
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Fundamentals to therapeutics: Epigenetic modulation of CD8+ T Cell exhaustion in the tumor microenvironment
TL;DR: In this paper , the background of T cell differentiation and various exhaustion states and how epigenetics play an important role in these processes are discussed and the most recent methodologies that are used to study and discover such epigenetic modulations.
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Exhausted T cells hijacking the cancer-immunity cycle: Assets and liabilities
TL;DR: In this paper , the contrary role of exhausted T cells is discussed, where the authors consider a tipping point where exhausted T-cells switch from an asset to a liability, which is referred to as T-cell exhaustion.
References
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