乳腺癌（BC）是一种高度异质性的疾病，虽然免疫治疗最近在多种实体肿瘤和血液肿瘤中提高了患者的生存率，但大多数BC亚型对免疫检查点阻断疗法（ICB）的反应较差。B细胞，特别是在三级淋巴结构（TLS）中集聚的B细胞，在抗肿瘤免疫中起着重要作用。然而，还需要进一步探索BC中单细胞分辨率的B细胞异质性以及其与TLS的临床意义。 从14名BC患者的原发肿瘤病灶和周围正常组织中获取了总计124,587个细胞进行单细胞转录组测序和生物信息学分析。基于通常的标记，将单细胞转录组文件归类到各种聚类簇中。我们进行了一项详细的单细胞研究，重点关注肿瘤浸润性B细胞（TIL-B）和肿瘤相关中性粒细胞（TAN）。TIL-B被分为五个簇，并且鉴定了与免疫治疗效果密切相关的滤泡状B细胞等异常细胞类型。在BC中，TAN和TIL-B浸润呈正相关，与TLS高组相比，TLS低组中的TAN和TIL-B呈显著正相关。 总之，我们的研究突显了BC中B细胞的异质性，解释了B细胞和TLS在单细胞和临床水平上如何显著贡献于抗肿瘤免疫，并提供了一个名为CD23的直接TLS标记。这些结果将为BC的肿瘤免疫治疗的适用性和有效性提供更相关的信息。 © 2023 The Authors. Clinical and Translational Medicine由上海临床生物信息学研究所的John Wiley & Sons Australia, Ltd代表出版。

Breast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic malignancies, most BC subtypes respond poorly to immune checkpoint blockade therapy (ICB). B cells, particularly those that congregate in tertiary lymphoid structures (TLS), play a significant role in antitumour immunity. However, B-cell heterogeneity at single-cell resolution and its clinical significance with TLS in BC need to be explored further.Primary tumour lesions and surrounding normal tissues were taken from 14 BC patients, totaling 124,587 cells, for single-cell transcriptome sequencing and bioinformatics analysis.Based on the usual markers, the single-cell transcriptome profiles were classified into various clusters. A thorough single-cell study was conducted with a focus on tumour-infiltrating B cells (TIL-B) and tumour-associated neutrophils (TAN). TIL-B was divided into five clusters, and unusual cell types, such as follicular B cells, which are strongly related to immunotherapy efficacy, were identified. In BC, TAN and TIL-B infiltration are positively correlated, and at the same time, compared with TLS-high, TAN and TIL-B in TLS-low group are significantly positively correlated.In conclusion, our study highlights the heterogeneity of B cells in BC, explains how B cells and TLS contribute significantly to antitumour immunity at both the single-cell and clinical level, and offers a straightforward marker for TLS called CD23. These results will offer more pertinent information on the applicability and effectiveness of tumour immunotherapy for BC.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.