Predictability of B cell clonal persistence and immunosurveillance in breast cancer.
Date
2024-05-01ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
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
Research team
Cancer Dynamics
Language
eng
Date accepted
2024-03-15
License start date
2024-05-01
Citation
Nature Immunology, 2024, 25 (5), pp. 916 - 924
Publisher
NATURE PORTFOLIO