DNA methylation makes for tired T cells

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Science  28 Jul 2017:
Vol. 357, Issue 6349, pp. 367-368
DOI: 10.1126/science.357.6349.367-f

T cell exhaustion is a phenomenon in chronic infections and cancer in which T cells express inhibitory receptors and stop working properly. One clinically applied approach to reversing this process has been to block the inhibitory receptor PD-1. However, T cells may resist such treatment as a result of transcriptional and epigenetic reprogramming. Ghoneim et al. found that progressive de novo DNA methylation is an essential process inaugurating CD8+ T cell exhaustion. This results in a distinct gene repression signature that is preserved during PD-1 blockade. The inhibition of DNA methylation before PD-1 blockade enhanced T cell rejuvenation and improved disease outcomes in mice. This approach offers hope of more effective treatments for viral infections and cancer.

Cell 170, 142 (2017).

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