Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling

Qingtao Hu, Yu Hong, Pan Qi, Guangqing Lu, Xueying Mai, Sheng Xu, Xiaoying He, Yu Guo, Linlin Gao, Zhiyi Jing, Jiawen Wang, Tao Cai and Yu Zhang ()
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Qingtao Hu: National Institute of Biological Sciences
Yu Hong: National Institute of Biological Sciences
Pan Qi: Xinxiang Central Hospital
Guangqing Lu: National Institute of Biological Sciences
Xueying Mai: National Institute of Biological Sciences
Sheng Xu: Xinxiang Central Hospital
Xiaoying He: Xinxiang Central Hospital
Yu Guo: Xinxiang Central Hospital
Linlin Gao: National Institute of Biological Sciences
Zhiyi Jing: National Institute of Biological Sciences
Jiawen Wang: National Institute of Biological Sciences
Tao Cai: National Institute of Biological Sciences
Yu Zhang: National Institute of Biological Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.

Date: 2021
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DOI: 10.1038/s41467-021-22300-2

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