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
Notes: Article -- Export Date: 3 July 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Jedd D Wolchok
    813 Wolchok
  2. Taha Merghoub
    291 Merghoub
  3. Agnes Viale
    231 Viale
  4. Christina Leslie
    142 Leslie
  5. Matthew David Hellmann
    333 Hellmann
  6. Andrew Crosbie Scott
    13 Scott
  7. Mary   Philip
    7 Philip
  8. Liping   Sun
    5 Sun
  9. Ellen Horste
    1 Horste
  10. Steven J Camara
    5 Camara