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

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 chrom...

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Autores principales: Wong, Wai Ki, Yin, Bohan, Lam, Ching Ying Katherine, Huang, Yingying, Yan, Jiaxiang, Tan, Zhiwu, Wong, Siu Hong Dexter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787221/
https://www.ncbi.nlm.nih.gov/pubmed/35087832
http://dx.doi.org/10.3389/fcell.2021.783227
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author Wong, Wai Ki
Yin, Bohan
Lam, Ching Ying Katherine
Huang, Yingying
Yan, Jiaxiang
Tan, Zhiwu
Wong, Siu Hong Dexter
author_facet Wong, Wai Ki
Yin, Bohan
Lam, Ching Ying Katherine
Huang, Yingying
Yan, Jiaxiang
Tan, Zhiwu
Wong, Siu Hong Dexter
author_sort Wong, Wai Ki
collection PubMed
description 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.
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spelling pubmed-87872212022-01-26 The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy Wong, Wai Ki Yin, Bohan Lam, Ching Ying Katherine Huang, Yingying Yan, Jiaxiang Tan, Zhiwu Wong, Siu Hong Dexter Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2022-01-11 /pmc/articles/PMC8787221/ /pubmed/35087832 http://dx.doi.org/10.3389/fcell.2021.783227 Text en Copyright © 2022 Wong, Yin, Lam, Huang, Yan, Tan and Wong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wong, Wai Ki
Yin, Bohan
Lam, Ching Ying Katherine
Huang, Yingying
Yan, Jiaxiang
Tan, Zhiwu
Wong, Siu Hong Dexter
The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy
title The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy
title_full The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy
title_fullStr The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy
title_full_unstemmed The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy
title_short The Interplay Between Epigenetic Regulation and CD8(+) T Cell Differentiation/Exhaustion for T Cell Immunotherapy
title_sort interplay between epigenetic regulation and cd8(+) t cell differentiation/exhaustion for t cell immunotherapy
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8787221/
https://www.ncbi.nlm.nih.gov/pubmed/35087832
http://dx.doi.org/10.3389/fcell.2021.783227
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