Ma Jiaqiang, Wu Yingcheng, Ma Lifeng, Yang Xupeng, Zhang Tiancheng, Song Guohe, Li Teng, Gao Ke, Shen Xia, Lin Jian, Chen Yamin, Liu Xiaoshan, Fu Yuting, Gu Xixi, Chen Zechuan, Jiang Shan, Rao Dongning, Pan Jiaomeng, Zhang Shu, Zhou Jian, Huang Chen, Shi Si, Fan Jia, Guo Guoji, Zhang Xiaoming, Gao Qiang
Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, and Stem Cell Institute, Zhejiang University, Hangzhou 310058, China.
Science. 2024 May 3;384(6695):eadj4857. doi: 10.1126/science.adj4857.
B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.
B淋巴细胞是体液免疫的重要介质，在人类癌症中发挥多种作用。为了解码肿瘤浸润B细胞的功能，我们生成了一个B细胞蓝图，涵盖了20种不同癌症类型（477个样本，269名患者）的单细胞转录组、B细胞受体库和染色质可及性数据。B细胞具有非凡的异质性，由15个亚群组成，可分为两条独立的发育路径（滤泡外与生发中心）。归入滤泡外路径的肿瘤类型与较差的临床结果和免疫治疗耐药性相关。功能失调的滤泡外程序通过表观遗传-代谢串扰与谷氨酰胺衍生的代谢物相关，这促进了T细胞驱动的免疫抑制程序。这些数据表明肿瘤内B细胞在滤泡外与生发中心反应之间存在平衡，并表明体液免疫可能可用于靶向B细胞的免疫治疗。
