Predictability of B cell clonal persistence and immunosurveillance in breast cancer
Sammut, Stephen-John (The Royal Marsden Hospital NHS Foundation Trust (Londres, Regne Unit))
Galson, Jacob D. (Alchemab Therapeutics (Whittlesford, Regne Unit))
Minter, Ralph (Alchemab Therapeutics (Whittlesford, Regne Unit))
Sun, Bo (University of Oxford)
Chin, Suet-Feung (University of Cambridge)
De Mattos-Arruda, Leticia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Finch, Donna K. (Alchemab Therapeutics (Whittlesford, Regne Unit))
Schätzle, Sebastian (Alchemab Therapeutics (Whittlesford, Regne Unit))
Dias, Jorge (Alchemab Therapeutics (Whittlesford, Regne Unit))
Rueda, Oscar M. (University of Cambridge)
Seoane Suárez, Joan (Vall d'Hebron Institut d'Oncologia)
Osbourn, Jane (Alchemab Therapeutics (Whittlesford, Regne Unit))
Caldas, Carlos (University of Cambridge)
Bashford-Rogers, Rachael (Oxford Cancer Centre, Oxford, UK)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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. In this Resource paper, the authors integrate T cell antigen receptor, B cell antigen receptor and exome sequencing comparing early and metastatic breast cancer in humans, showing how the immune response and tumors coevolve.
Ajuts:	European Commission 694620
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Immunoediting ; Clonal selection ; Immunological surveillance
Publicat a:	Nature immunology, Vol. 25 (may 2024) , p. 916-924, ISSN 1529-2916

DOI: 10.1038/s41590-024-01821-0
PMID: 38698238

25 p, 8.9 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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