T Cell Exhaustion: An Epigenetically Imprinted Phenotypic and Functional Makeover

A recent article in Cell demonstrates that the absence of a single DNA methyltransferase, Dnmt3a, prevents cytotoxic T cells from acquiring the hypofunctional or exhausted phenotype typically seen in chronic viral infections and tumors. Upon establishing a causal relationship between exhaustion-associated epigenetic changes and reduced CD8+ T cell function, the authors provided mechanistic evidence that exhaustion constitutes a specific differentiation program. A recent article in Cell demonstrates that the absence of a single DNA methyltransferase, Dnmt3a, prevents cytotoxic T cells from acquiring the hypofunctional or exhausted phenotype typically seen in chronic viral infections and tumors. Upon establishing a causal relationship between exhaustion-associated epigenetic changes and reduced CD8+ T cell function, the authors provided mechanistic evidence that exhaustion constitutes a specific differentiation program. De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell RejuvenationGhoneim et al.CellJune 22, 2017In BriefDe novo DNA methylation programs promote T cell exhaustion, and inhibiting these programs can enhance immune-checkpoint-blockade-mediated T cell rejuventation and ultimately facilitate the control of chronic viral infections and tumor growth. Full-Text PDF Open Archive