Predictability of B cell clonal persistence and immunosurveillance in breast cancer

Nat Immunol. 2024 May;25(5):916-924. doi: 10.1038/s41590-024-01821-0. Epub 2024 May 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Neoplasm / immunology
  • B-Lymphocytes* / immunology
  • Breast Neoplasms* / immunology
  • Clone Cells
  • Exome Sequencing
  • Female
  • Humans
  • Immunologic Surveillance*
  • Monitoring, Immunologic
  • Neoplasm Metastasis
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology


  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, B-Cell
  • Antigens, Neoplasm