Chromatin states define tumour-specific T cell dysfunction and reprogramming
| العنوان: | Chromatin states define tumour-specific T cell dysfunction and reprogramming |
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| المؤلفون: | Mojdeh Shakiba, Mary Philip, Taha Merghoub, Peter Lauer, Agnes Viale, Steven Camara, Matthew D. Hellmann, Liping Sun, Christina S. Leslie, Andrea Schietinger, Andrew Scott, Lauren Fairchild, Jedd D. Wolchok, Ellen L. Horste |
| المصدر: | Nature |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, T cell, medicine.medical_treatment, CD8-Positive T-Lymphocytes, Biology, Article, Epigenesis, Genetic, Mice, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Cancer immunotherapy, Neoplasms, medicine, Animals, Humans, Cytotoxic T cell, Epigenetics, Multidisciplinary, Gene Expression Profiling, Immunotherapy, Chromatin, Immune checkpoint, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, Female, Immunologic Memory, Reprogramming, Transcription Factors, 030215 immunology |
| الوصف: | 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. |
| تدمد: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature22367 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0503e979c72b7d675a1422690382887e https://doi.org/10.1038/nature22367 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0503e979c72b7d675a1422690382887e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764687 00280836 |
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| DOI: | 10.1038/nature22367 |