Predictability of B cell clonal persistence and immunosurveillance in breast cancer.

Sammut S-J., Galson JD., Minter R., Sun B., Chin S-F., De Mattos-Arruda L., Finch DK., Schätzle S., Dias J., Rueda OM., Seoane J., Osbourn J., Caldas C., Bashford-Rogers RJM.

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.

DOI

10.1038/s41590-024-01821-0

Type

Journal article

Publication Date

2024-05-01T00:00:00+00:00

Volume

25

Pages

916 - 924

Total pages

8

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

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