miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate

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• dc.contributor.author Ji, Yun
• dc.contributor.author Di Croce, Luciano
• dc.contributor.author Gattinoni, Luca
• dc.date.accessioned 2019-07-30T07:42:32Z
• dc.date.available 2019-07-30T07:42:32Z
• dc.date.issued 2019
• dc.description.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.
• dc.description.sponsorship This research was supported by the Intramural Research Programs of the US National Institutes of Health, National Cancer Institute (ZIABC011480)
• dc.format.mimetype application/pdf
• dc.identifier.citation Ji Y, Fioravanti J, Zhu W, Wang H, Wu T, Hu J et al. miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate. Nat Commun. 2019 May 14;10(1):2157. DOI: 10.1038/s41467-019-09882-8
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-09882-8
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/42200
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Communications. 2019 May 14;10(1):2157
• dc.rights © Springer Nature Publishing AG. http://dx.doi.org/10.1038/s41467-019-09882-8. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Cèl·lules T
• dc.subject.other Melanoma
• dc.subject.other MicroARN
• dc.subject.other Pell -- Tumors
• dc.subject.other Factors de transcripció
• dc.subject.other Immunologia
• dc.title miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion