Chromatin states define tumour-specific T cell dysfunction and reprogramming Journal Article
| Authors: | Philip, M.; Fairchild, L.; Sun, L.; Horste, E. L.; Camara, S.; Shakiba, M.; Scott, A. C.; Viale, A.; Lauer, P.; Merghoub, T.; Hellmann, M. D.; Wolchok, J. D.; Leslie, C. S.; Schietinger, A. |
| Article Title: | 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 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. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
| Keywords: | mus |
| Journal Title: | Nature |
| Volume: | 545 |
| Issue: | 7655 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-05-25 |
| Start Page: | 452 |
| End Page: | 456 |
| Language: | English |
| DOI: | 10.1038/nature22367 |
| PROVIDER: | scopus |
| PUBMED: | 28514453 |
| PMCID: | PMC5693219 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 July 2017 -- Source: Scopus |
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