A blueprint for tumor-infiltrating B cells across human cancers

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-05-03 DOI:10.1126/science.adj4857

Jiaqiang Ma, Yingcheng Wu, Lifeng Ma, Xupeng Yang, Tiancheng Zhang, Guohe Song, Teng Li, Ke Gao, Xia Shen, Jian Lin, Yamin Chen, Xiaoshan Liu, Yuting Fu, Xixi Gu, Zechuan Chen, Shan Jiang, Dongning Rao, Jiaomeng Pan, Shu Zhang, Jian Zhou, Chen Huang, Si Shi, Jia Fan, Guoji Guo, Xiaoming Zhang, Qiang Gao

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Abstract

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.

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人类癌症中肿瘤浸润 B 细胞的蓝图

B 淋巴细胞是体液免疫的重要介质，在人类癌症中发挥着多种作用。为了解读肿瘤浸润 B 细胞的功能，我们生成了一个 B 细胞蓝图，其中包括 20 种不同癌症类型（477 个样本，269 名患者）的单细胞转录组、B 细胞受体谱系和染色质可及性数据。B细胞具有非同寻常的异质性，由15个亚群组成，可分为两种独立的发育途径（滤泡外与生殖中心）。被归入卵泡外途径的肿瘤类型与较差的临床疗效和对免疫疗法的抗药性有关。功能失调的小叶外程序通过表观遗传-代谢交叉对话与谷氨酰胺衍生代谢物有关，这促进了T细胞驱动的免疫抑制程序。这些数据表明了肿瘤内B细胞在卵泡外和生殖中心反应之间的平衡，并表明体液免疫有可能被用于B细胞靶向免疫疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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