中山大学孙逸仙纪念医院苏士成团队取得一项重要进展，他们的最新工作发现，补体信号决定B细胞在化疗诱导免疫中的相反作用。3月5日，论文在线发表于《细胞》。

通过对乳腺癌新辅助化疗前后患者纵向样本中的B细胞异质性进行单细胞测序，研究人员发现ICOSL⁺B细胞亚群在化疗后出现。使用三种具有免疫功能的小鼠模型，研究人员描述了化疗中人肿瘤浸润B细胞的亚型开关。

通过使用B细胞特异性敲除小鼠，他们表明B细胞中的ICOSL通过增强效应与调节性T细胞的比例来增强抗肿瘤免疫力。ICOSL⁺B细胞的特征被补体CR2信号所标记，该信号由免疫原性细胞死亡所触发。

此外，研究人员确定了补体抑制蛋白CD55决定B细胞在化疗中的相反作用。因此，研究人员证明了B细胞亚群开关在化疗反应中的关键作用，这在设计新型抗癌疗法中具有意义。

研究人员介绍，了解决定B细胞多样性的分子机制对于靶向B细胞作为抗癌治疗非常重要。

更多阅读

苏士成，）

附：英文原文

Title: Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity

Author: Yiwen Lu, Qiyi Zhao, Jian-You Liao, Erwei Song, Qidong Xia, Jiayao Pan, Yihong Li, Jiaqian Li, Boxuan Zhou, Yingying Ye, Can Di, Shubin Yu, Yunjie Zeng, Shicheng Su

Issue&Volume: 2020-03-05

Abstract: Understanding molecular mechanisms that dictate B cell diversity is important fortargeting B cells as anti-cancer treatment. Through the single-cell dissection ofB cell heterogeneity in longitudinal samples of patients with breast cancer beforeand after neoadjuvant chemotherapy, we revealed that an ICOSL+ B cell subset emerges after chemotherapy. Using three immunocompetent mouse models,we recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy.By employing B-cell-specific deletion mice, we showed that ICOSL in B cells boostsanti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signatureof ICOSL+ B cells is imprinted by complement-CR2 signaling, which is triggered by immunogeniccell death. Moreover, we identified that CD55, a complement inhibitory protein, determinesthe opposite roles of B cells in chemotherapy. Collectively, we demonstrated a criticalrole of the B cell subset switch in chemotherapy response, which has implicationsin designing novel anti-cancer therapies.

DOI: 10.1016/j.cell.2020.02.015

编辑：小柯机器人