美国圣犹德儿童研究医院Douglas R. Green、Hongbo Chi等研究人员合作发现,cBAF复合体成分和MYC在CD8+T细胞命运的早期中合作。该项研究成果于2022年6月22日在线发表在《自然》杂志上。
Author: 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.
Issue&Volume: 2022-06-22
Abstract: The identification of mechanisms to promote memory T (Tmem) cells has important implications for vaccination and anti-cancer immunotherapy1,2,3,4. Using a CRISPR-based screen for negative regulators of Tmem cell 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 Tmem cell formation in vivo. During the first division of activated CD8+ T cells, cBAF and MYC8 frequently co-assort asymmetrically to the two daughter cells. Daughter cells with high MYC and high cBAF display a cell fate trajectory towards Teff cells, whereas those with low MYC and low cBAF preferentially differentiate towards Tmem cells. 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 48h 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 Tmem cell fate and suggest that manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.
DOI: 10.1038/s41586-022-04849-0
Source: https://www.nature.com/articles/s41586-022-04849-0
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
本期文章:《自然》:Online/在线发表