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Review | Open Access

Exhausted T cells and epigenetic status

Ziqing Zeng1, Feng Wei1, Xiubao Ren1,2 ( )
Department of Immunology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China
Department of Biotherapy Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China
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Abstract

Exhausted T cells are a group of dysfunctional T cells, which are present in chronic infections or tumors. The most significant characteristics of exhausted T cells are attenuated effector cytotoxicity, reduced cytokine production, and upregulation of multiple inhibitory molecular receptors (e.g., PD-1, TIM-3, and LAG-3). The intracellular metabolic changes, altered expression of transcription factors, and a unique epigenetic landscape constitute the exhaustion program. Recently, researchers have made progress in understanding exhausted T cells, with the definition and identification of exhausted T cells changing from phenotype-based to being classified at the transcriptional and epigenetic levels. Recent studies have revealed that exhausted T cells can be separated into two subgroups, namely TCF1+PD-1+ progenitor-like precursor exhausted cells and TCF1-PD-1+ terminally differentiated exhausted T cells. Moreover, the progenitor-like precursor cell population may be a subset of T cells that can respond to immunotherapy. Studies have also found that TOX initiates and dominates the development of exhausted T cells at the transcriptional and epigenetic levels. TOX also maintains T cell survival and may affect decisions regarding treatment strategies. In this review, we discuss the latest developments in T cell exhaustion in regards to definitions, subpopulations, development mechanisms, differences in diverse diseases, and treatment prospects for exhausted T cells. Furthermore, we hypothesize that the epigenetic state regulated by TOX might be the key point, which can determine the reversibility of exhaustion and the efficacy of immunotherapy.

Keywords

immunotherapytumor immunityT cell exhaustionTOXepigenetic landscape

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Cancer Biology & Medicine
Volume 17 Issue 4,
November 2020
Pages 923-936
DOI: 10.20892/j.issn.2095-3941.2020.0338
Cite this article:
Zeng Z, Wei F, Ren X. Exhausted T cells and epigenetic status. Cancer Biology & Medicine, 2020, 17(4): 923-936. https://doi.org/10.20892/j.issn.2095-3941.2020.0338

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Received: 25 June 2020
Accepted: 07 September 2020
Published: 15 November 2020
©2020 Cancer Biology & Medicine.

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