Dynamic chromatin regulatory landscape of human CAR T cell exhaustion

著者: David Gennert, Rachel C. Lynn, Jeff M. Granja, Evan Weber, Maxwell R. Mumbach, Yang Zhao, Zhana Duren, Elena Sotillo, William J. Greenleaf, Wing Hung Wong, Ansuman T. Satpathy, Crystal L. Mackall, Howard Y. Chang - Proceedings of the National Academy of Sciences, PNAS 2021 被引用: 65

Significance T cell exhaustion is a major barrier to cancer immunotherapy. T cell exhaustion is the state of T cell dysfunction after chronic stimulation, and recent studies indicate that exhaustion is epigenetically controlled and associated with unique chromatin profiles. This work reports the genome-wide map of active DNA regulatory elements and their connection to genes in the time course of human chimeric antigen receptor T cell exhaustion. Early chromatin events establish the later program of gene expression, active elements are often human-specific, and exhaustion-associated enhancers can be manipulated to precisely control the level of inhibitory receptors on T cells.