The Interplay Between Epigenetic Regulation and CD8+ T Cell Differentiation/Exhaustion for T Cell Immunotherapy

Wai Ki Wong, Bohan Yin, Ching Ying Katherine Lam, Yingying Huang, Jiaxiang Yan, Zhiwu Tan, Siu Hong Dexter Wong

Research output: Journal article publicationReview articleAcademic researchpeer-review

12 Citations (Scopus)

Abstract

Effective immunotherapy treats cancers by eradicating tumourigenic cells by activated tumour antigen-specific and bystander CD8+ T-cells. However, T-cells can gradually lose cytotoxicity in the tumour microenvironment, known as exhaustion. Recently, DNA methylation, histone modification, and chromatin architecture have provided novel insights into epigenetic regulations of T-cell differentiation/exhaustion, thereby controlling the translational potential of the T-cells. Thus, developing strategies to govern epigenetic switches of T-cells dynamically is critical to maintaining the effector function of antigen-specific T-cells. In this mini-review, we 1) describe the correlation between epigenetic states and T cell phenotypes; 2) discuss the enzymatic factors and intracellular/extracellular microRNA imprinting T-cell epigenomes that drive T-cell exhaustion; 3) highlight recent advances in epigenetic interventions to rescue CD8+ T-cell functions from exhaustion. Finally, we express our perspective that regulating the interplay between epigenetic changes and transcriptional programs provides translational implications of current immunotherapy for cancer treatments.

Original languageEnglish
Article number783227
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - 11 Jan 2022

Keywords

  • adoptive immunotherapy
  • epigenetic regulation
  • T-cell activation
  • T-cell differentiation
  • T-cell exhaustion

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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