Ontology type: schema:ScholarlyArticle Open Access: True
2017-05-17
AUTHORSMary Philip, Lauren Fairchild, Liping Sun, Ellen L. Horste, Steven Camara, Mojdeh Shakiba, Andrew C. Scott, Agnes Viale, Peter Lauer, Taha Merghoub, Matthew D. Hellmann, Jedd D. Wolchok, Christina S. Leslie, Andrea Schietinger
ABSTRACTTumour-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 PD1hi dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1hi tumour-infiltrating CD8 T cells. Our study has important implications for cancer immunotherapy as we define key transcription factors and epigenetic programs underlying T cell dysfunction and surface markers that predict therapeutic reprogrammability. More... »
PAGES452-456
http://scigraph.springernature.com/pub.10.1038/nature22367
DOIhttp://dx.doi.org/10.1038/nature22367
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