دورية
cBAF complex components and MYC cooperate early in CD8+T cell fate
| العنوان: | cBAF complex components and MYC cooperate early in CD8+T cell fate |
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| المؤلفون: | Guo, Ao, Huang, Hongling, Zhu, Zhexin, Chen, Mark J., Shi, Hao, Yuan, Sujing, Sharma, Piyush, Connelly, Jon P., Liedmann, Swantje, Dhungana, Yogesh, Li, Zhenrui, Haydar, Dalia, Yang, Mao, Beere, Helen, Yustein, Jason T., DeRenzo, Christopher, Pruett-Miller, Shondra M., Crawford, Jeremy Chase, Krenciute, Giedre, Roberts, Charles W. M., Chi, Hongbo, Green, Douglas R. |
| المصدر: | Nature; 20240101, Issue: Preprints p1-7, 7p |
| مستخلص: | The identification of mechanisms to promote memory T (Tmem) cells has important implications for vaccination and anti-cancer immunotherapy1–4. Using a CRISPR-based screen for negative regulators of Tmemcell generation in vivo5, here we identify multiple components of the mammalian canonical BRG1/BRM-associated factor (cBAF)6,7. Several components of the cBAF complex are essential for the differentiation of activated CD8+T cells into T effector (Teff) cells, and their loss promotes Tmemcell formation in vivo. During the first division of activated CD8+T cells, cBAF and MYC8frequently co-assort asymmetrically to the two daughter cells. Daughter cells with high MYC and high cBAF display a cell fate trajectory towards Teffcells, whereas those with low MYC and low cBAF preferentially differentiate towards Tmemcells. The cBAF complex and MYC physically interact to establish the chromatin landscape in activated CD8+T cells. Treatment of naive CD8+T cells with a putative cBAF inhibitor during the first 48 h of activation, before the generation of chimeric antigen receptor T (CAR-T) cells, markedly improves efficacy in a mouse solid tumour model. Our results establish cBAF as a negative determinant of Tmemcell fate and suggest that manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy. |
| قاعدة البيانات: | Supplemental Index |
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Full Text Finder | تدمد: | 00280836 14764687 |
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| DOI: | 10.1038/s41586-022-04849-0 |