Predictability of B cell clonal persistence and immunosurveillance in breast cancer
Stephen‐John Sammut, Jacob D. Galson, Ralph Minter, Bo Sun, Suet‐Feung Chin, Leticia De Mattos‐Arruda, Donna K. Finch, Sebastian Schätzle, J.C. Dias, Oscar M. Rueda, Joan Seoane, Jane Osbourn, Carlos Caldas, Rachael Bashford-Rogers
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.