Understanding molecular mechanisms that dictate B cell diversity is important for targeting B cells as anti-cancer treatment. Through the single-cell dissection of B cell heterogeneity in longitudinal samples of patients with breast cancer before and 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 boosts anti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signature of ICOSL⁺ B cells is imprinted by complement-CR2 signaling, which is triggered by immunogenic cell death. Moreover, we identified that CD55, a complement inhibitory protein, determines the opposite roles of B cells in chemotherapy. Collectively, we demonstrated a critical role of the B cell subset switch in chemotherapy response, which has implications in designing novel anti-cancer therapies.

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中文翻译：

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补体信号确定B细胞在化疗诱导的免疫中的相反作用。

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。通过对乳腺癌新辅助化疗前后的患者纵向样本中的B细胞异质性进行单细胞解剖，我们发现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，我们概述了化疗期间人肿瘤浸润B细胞的亚组开关。通过采用B细胞特异性删除小鼠，我们表明B细胞中的ICOSL通过增强效应子与调节性T细胞的比例来增强抗肿瘤免疫力。ICOSL的签名⁺B细胞被补体CR2信号转导，该信号由免疫原性细胞死亡触发。此外，我们确定了补体抑制蛋白CD55决定了B细胞在化疗中的相反作用。集体地，我们证明了B细胞亚群转换在化学疗法反应中的关键作用，这在设计新颖的抗癌疗法中具有意义。

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