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Cancer immunotherapy

Epigenetic checkpoints regulate the fate and function of CAR-T cells

T cells exist in many functional states, and dynamic transitions from one state to another affect the outcome of adoptive T cell therapy. FOXP1 and KLF2 are now identified as transcriptional regulators of the stemness of CD8+ CAR-T cells and the bifurcation of stem-like CD8+ CAR-T cells into effector and exhausted subsets, respectively.

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Fig. 1: FOXP1 and KLF2 are key regulators of CAR-T cell fate.

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Correspondence to Eliana Ruggiero.

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Competing interests

M.C., C.B. and E.R. are inventors on different patents on cancer immunotherapy and genome editing (E.R.: PCT/EP2018/060477, PCT/EP2019/079916 and PCT/EP2022/053040; C.B.: PCT/IT2006/000600, 12/927,292, PCT/US2014/031360, PCT/IB2015/057049, PCT/EP2018/060477, PCT/EP2019/079916, PCT/EP2021/061198 and PCT/EP2022/053040; M.C.: PCT/IB2015/057049, PCT/EP2021/061198 and PCT/EP2019/069712). M.C. has received research support from Kite/Gilead. C.B. has been a member of advisory boards and a consultant for Intellia Therapeutics, TxCell, Novartis, GSK, Allogene, Kite/Gilead, Miltenyi, Kiadis and Janssen, and received research support from Intellia Therapeutics.

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Casucci, M., Bonini, C. & Ruggiero, E. Epigenetic checkpoints regulate the fate and function of CAR-T cells. Nat Immunol 25, 4–6 (2024). https://doi.org/10.1038/s41590-023-01708-6

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