miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate
Year: 2019
Type: article
Abstract: T cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here we show that miR-155 increases CD8 + T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of terminal differentiation. miR-155 enhances Polycomb repressor complex 2 (PRC2) activity indirectly by promoting the expression of the PRC2-associated factor Phf19 through downregulation of the Akt inhibitor, Ship1. Phf19 orchestrates a transcriptional program extensively shared with miR-155 to restrain T cell senescence and sustain CD8 + T cell antitumor responses. These effects rely on Phf19 histone-binding capacity, which is critical for the recruitment of PRC2 to the target chromatin. These findings establish the miR-155–Phf19–PRC2 as a pivotal axis regulating CD8 + T cell differentiation, thereby paving new ways for potentiating cancer immunotherapy through epigenetic reprogramming of CD8 + T cell fate.
Source: Nature Communications
Authors: Yun Ji, Jessica Fioravanti, Wei Zhu, Hongjun Wang, Tuoqi Wu, Jinhui Hu, Neal E. Lacey, Sanjivan Gautam, John B. Le Gall, Xia Yang, James D. Hocker, Thelma M. Escobar, Shan He, Stefania Dell’Orso, Nga V. Hawk, Veena Kapoor, William G. Telford, Luciano Di Croce, Stefan A. Muljo, Yi Zhang, Vittorio Sartorelli, Luca Gattinoni
Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, Temple University, Institució Catalana de Recerca i Estudis Avançats, Universitat Pompeu Fabra, Barcelona Institute of Science and Technology, Centre for Genomic Regulation
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
OpenAlex ID: W2946088529