近日，复旦大学储以微、刘荣花等研究人员合作发现，表达亮氨酸tRNA合成酶2的B细胞有助于结直肠癌的免疫逃逸。相关论文于2022年6月3日在线发表在《免疫》杂志上。

Author: Zhiqiang Wang, Zhou Lu, Shengli Lin, Jie Xia, Ziwen Zhong, Zhangjuan Xie, Yun Xing, Jingbo Qie, Mengxia Jiao, Yifan Li, Haoyu Wen, Pengyuan Zhao, Dan Zhang, Pinghong Zhou, Jiawen Qian, Feifei Luo, Luman Wang, Hongxiu Yu, Jie Liu, Jie Gu, Ronghua Liu, Yiwei Chu

Issue&Volume: 2022-06-03

Abstract: Immunoregulatory B cells impede antitumor immunity through unknown features and mechanisms. We report the existence of leucine-tRNA-synthase-2 (LARS2)-expressing B cell (LARS B) subset with a transforming growth factor-β1 (TGF-β1)-dominant regulatory feature in both mouse and human progressive colorectal cancer (CRC). Of note, LARS B cells exhibited a leucine nutrient preference and displayed active mitochondrial aminoacyl-tRNA biosynthesis. They were located outside the tertiary lymphoid structure and correlated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet induced LARS B cell generation, whereas LARS B cell deletion by Lars2 gene ablation or leucine blockage repressed CRC immunoevasion. Mechanistically, LARS2 programmed mitochondrial nicotinamide adenine dinucleotide (NAD+) regeneration and oxidative metabolism, thus determining the regulatory feature of LARS B cells in which the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) was involved. We propose a leucine-dieting scheme to inhibit LARS B cells, which is safe and useful for CRC therapy.

DOI: 10.1016/j.immuni.2022.04.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00188-1