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

Stephen-John SammutJacob D GalsonRalph MinterBo SunSuet-Feung ChinLeticia De Mattos-ArrudaDonna K FinchSebastian SchätzleJorge DiasOscar M RuedaJoan SeoaneJane OsbournCarlos CaldasRachael J M Bashford-Rogers
Published in: Nature immunology (2024)
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.
Keyphrases
  • papillary thyroid
  • squamous cell
  • squamous cell carcinoma
  • small cell lung cancer
  • metastatic breast cancer
  • early breast cancer
  • childhood cancer
  • lymph node
  • stem cells
  • locally advanced
  • drug delivery
  • network analysis