Single‐cell transcriptome sequencing of B‐cell heterogeneity and tertiary lymphoid structure predicts breast cancer prognosis and neoadjuvant therapy efficacy

作者：Qing Wang, Ke Sun, Rui Liu, Ying Song, Yafeng Lv, Pingping Bi, Fuying Yang, Sijia Li, Jiawen Zhao, Xiuqin Li, Dong Chen, Jialin Mei, Rirong Yang, Kai Chen, Dequan Liu, Shicong Tang · 发表于：Clinical and Translational Medicine · 年份：2023 · DOI：10.1002/ctm2.1346 · 被引用次数：99 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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...