2026-04-14T05:40:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/422002025-12-12T02:27:18Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Ji, Yun author Di Croce, Luciano author Gattinoni, Luca author 2019-07-30T07:42:32Z 2019-07-30T07:42:32Z 2019 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. This research was supported by the Intramural Research Programs of the US National Institutes of Health, National Cancer Institute (ZIABC011480) Cèl·lules T Melanoma MicroARN Pell -- Tumors Factors de transcripció Immunologia miR-155 harnesses Phf19 to potentiate cancer immunotherapy through epigenetic reprogramming of CD8+ T cell fate