Chromatin states define tumor-specific T cell dysfunction and reprogramming
By M. Philip, Lauren Fairchild, Liping Sun, Ellen L. Horste, Steven Camara, M. Shakiba, A. Scott, A. Viale, P. Lauer, T. Merghoub and 4 more. Nature, 2017
829 citations recorded by the source corpus.
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.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/3b0d0dd9431f953606de38ca16e597b4304de9f3
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Citations in the corpus
- T Cell Dysfunction in Cancer (2018, background): “E urope PM C Funders A uthor M anuscripts E urope PM C Funders A uthor M anuscripts (Philip et al., 2017).”
- Engineering strategies to overcome the current roadblocks in CAR T cell therapy (2019, background): “For example, disease-related dysfunctions of T cells 217 , such as those described in patients with CLL 218,219 or solid tumours 220 , can result in unsuccessful manufacturing or inferior products that lead to poor response rates in patients.”