Predictability of B cell clonal persistence and immunosurveillance in breast cancer
Por:
Sammut, SJ, Galson, JD, Minter, R, Sun, B, Chin, SF, De Mattos-Arruda, L, Finch, DK, Schätzle, S, Dias, J, Rueda, OM, Seoane, J, Osbourn, J, Caldas, C and Bashford-Rogers, RJM
Publicada:
1 may 2024
Resumen:
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.
Filiaciones:
Sammut, SJ:
Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London, England
Royal Marsden Hosp NHS Fdn Trust, London, England
Galson, JD:
Alchemab Therapeut, Whittlesford, England
Minter, R:
Alchemab Therapeut, Whittlesford, England
Sun, B:
Wellcome Ctr Human Genet, Oxford, England
Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England
Chin, SF:
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
:
Germans Trias & Pujol Univ Hosp, IrsiCaixa, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Badalona, Spain
Finch, DK:
Alchemab Therapeut, Whittlesford, England
Schätzle, S:
Alchemab Therapeut, Whittlesford, England
Dias, J:
Alchemab Therapeut, Whittlesford, England
Rueda, OM:
Univ Cambridge, MRC Biostat Unit, Cambridge, England
Seoane, J:
Vall dHebron Univ Hosp, Univ Autonoma Barcelona UAB, Vall dHebron Inst Oncol VHIO, Inst Catalana Recerca & Estudis Avancats ICREA,CIB, Barcelona, Spain
Osbourn, J:
Alchemab Therapeut, Whittlesford, England
Caldas, C:
Univ Cambridge, Sch Clin Med, Cambridge, England
Bashford-Rogers, RJM:
Wellcome Ctr Human Genet, Oxford, England
Univ Oxford, Dept Biochem, Oxford, England
Oxford Canc Ctr, Oxford, England
hybrid
|