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Predictability of B cell clonal persistence and immunosurveillance in breast cancer

Authors: Sammut, S-J; Galson, JD; Minter, R; Sun, B; Chin, S-F; De Mattos-Arruda, L; Finch, DK; +7 Authors

Predictability of B cell clonal persistence and immunosurveillance in breast cancer

Abstract

AbstractB 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.

Keywords

Resource, Monitoring, Cèl·lules B, T-Lymphocytes, Receptors, Antigen, T-Cell, 610, Receptors, Antigen, B-Cell, Breast Neoplasms, Immunitat cel·lular, Immunoediting, Mama - Càncer, Immunologic, Monitoring, Immunologic, Antigens, Neoplasm, Receptors, Exome Sequencing, Humans, Antigens, Neoplasm Metastasis, Immunologic Surveillance, B-Lymphocytes, PHENOMENA AND PROCESSES::Immune System Phenomena::Immunity::Adaptive Immunity::Immunity, Cellular::Immunologic Surveillance, B-Cell, Immunological surveillance, T-Cell, ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes, Clone Cells, ANATOMÍA::células::células productoras de anticuerpos::linfocitos B, Clonal selection, FENÓMENOS Y PROCESOS::fenómenos del sistema inmunitario::inmunidad::inmunidad adaptativa::inmunidad celular::vigilancia inmunológica, Antigen, Neoplasm, Female, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
11
Top 10%
Average
Top 10%
Green
hybrid