Chromatin states define tumour-specific T cell dysfunction and reprogramming.

ABSTRACT: Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours to progress. The epigenetic regulation of T cell dysfunction and therapeutic reprogrammability (for example, to immune checkpoint blockade) is not well understood. Here we show that T cells in mouse tumours differentiate through two discrete chromatin states: a plastic dysfunctional state from which T cells can be rescued, and a fixed dysfunctional state in which the cells are resistant to reprogramming. We identified surface markers associated with each chromatin state that distinguished reprogrammable from non-reprogrammable PD1^hi dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1^hi tumour-infiltrati

SUBMITTER: Philip M 

PROVIDER: S-EPMC5693219 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature