Year: 2024
Type: article
Study design: Observational Study
Abstract: 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.
Source: Nature Immunology
Institutions: Royal Marsden NHS Foundation Trust, Institute of Cancer Research, Breast Cancer Now, Royal Marsden Hospital, Centre for Human Genetics, University of Oxford, University of Cambridge, Cancer Research UK, IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol, MRC Biostatistics Unit, Institució Catalana de Recerca i Estudis Avançats, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital Universitari, Centro de Investigación Biomédica en Red de Cáncer, Vall d'Hebron Institute of Oncology, Cancer Research UK Oxford Centre
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
Funders: Fundación Cellex, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, British Medical Association, Academy of Medical Sciences, University of Oxford, Fundació Institut de Recerca Hospital Universitari Vall d’Hebron, Medical Research Council, NIHR Cambridge Biomedical Research Centre, H2020 European Research Council
OpenAlex ID: W4396592809