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Exhausted T cells and epigenetic status.

Ziqing Zeng1, Feng Wei1, Xiubao Ren1,2

  • 1Department 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.

Cancer Biology & Medicine
|December 10, 2020
PubMed
Summary

T cell exhaustion, characterized by dysfunctional T cells in chronic diseases, is increasingly defined by transcriptional and epigenetic factors. The transcription factor TOX plays a key role in T cell exhaustion development and may influence immunotherapy effectiveness.

Keywords:
T cell exhaustionTOXepigenetic landscapeimmunotherapytumor immunity

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Area of Science:

  • Immunology
  • Cellular Biology
  • Cancer Research

Background:

  • T cell exhaustion is a state of T cell dysfunction observed in chronic infections and tumors.
  • Key features include reduced cytotoxicity, diminished cytokine production, and expression of inhibitory receptors like PD-1, TIM-3, and LAG-3.
  • The exhaustion program involves metabolic alterations, transcription factor changes, and a distinct epigenetic landscape.

Purpose of the Study:

  • To review recent advancements in understanding T cell exhaustion.
  • To discuss evolving definitions, subpopulations, developmental mechanisms, disease-specific differences, and therapeutic strategies.
  • To explore the role of TOX and epigenetic regulation in T cell exhaustion reversibility and immunotherapy response.

Main Methods:

  • Literature review of recent studies on T cell exhaustion.
  • Analysis of transcriptional and epigenetic profiling data.
  • Discussion of findings related to T cell subpopulations and transcription factor roles.

Main Results:

  • T cell exhaustion is now classified at transcriptional and epigenetic levels, moving beyond phenotypic definitions.
  • Two distinct subpopulations identified: progenitor-like TCF1+PD-1+ and terminally differentiated TCF1-PD-1+ exhausted T cells.
  • The transcription factor TOX is crucial for initiating and maintaining T cell exhaustion, impacting survival and treatment decisions.

Conclusions:

  • The epigenetic state regulated by TOX is hypothesized to be critical for determining the reversibility of T cell exhaustion.
  • Understanding T cell subpopulations and TOX-mediated epigenetic regulation may enhance immunotherapy efficacy.
  • Further research into these mechanisms could lead to improved treatment strategies for chronic infections and cancers.