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B cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy. Using immune receptor, RNA and whole-exome sequencing, we show that both B cell and T cell responses seem to coevolve with the metastatic cancer genomes and mirror tumor mutational and neoantigen architecture. B cell clones associated with metastatic immunosurveillance and temporal persistence were more expanded and distinct from site-specific clones. B cell clonal immunosurveillance and temporal persistence are predictable from the clonal structure, with higher-centrality B cell antigen receptors more likely to be detected across multiple metastases or across time. This predictability was generalizable across other immune-mediated disorders. This work lays a foundation for prioritizing antibody sequences for therapeutic targeting in cancer.

Original publication

DOI

10.1038/s41590-024-01821-0

Type

Journal article

Journal

Nat Immunol

Publication Date

05/2024

Volume

25

Pages

916 - 924

Keywords

Humans, Female, Breast Neoplasms, B-Lymphocytes, Immunologic Surveillance, Receptors, Antigen, T-Cell, Receptors, Antigen, B-Cell, T-Lymphocytes, Monitoring, Immunologic, Exome Sequencing, Antigens, Neoplasm, Neoplasm Metastasis, Clone Cells