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. 2021 Mar 30;12:652160. doi: 10.3389/fimmu.2021.652160

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Copyright © 2021 Maes, Mondino, Lasarte, Agirre, Vanderkerken, Prosper and Breckpot

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.

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Epigenetics and T cell exhaustion. T cell exhaustion is characterized by reduced T cell proliferation, effector functions and increased expression of inhibitory receptors such as PD-1, CTLA-4 and TIM-3. The expression of these inhibitory receptors in CD8⁺ tumor-infiltrating cells is enabled altered chromatin accessibility and binding of transcription factors such as NFAT, TOX, NR4A, T-bet, Sox1 and Rara in genes exerting a negative role for T function. In addition, DNMT3A mediates DNA methylation and silencing of effector genes, hence serving as a potential target to reverse T cell exhaustion. IR, inhibitory receptor.