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.

B细胞和T细胞是适应性免疫系统的重要组成部分，介导抗癌免疫。癌症中的 T 细胞景观已得到很好的表征，但 B 细胞对抗癌免疫监视的贡献却鲜为人知。在这里，我们展示了新辅助治疗期间转移性乳腺癌个体和早期乳腺癌个体的 B 细胞和 T 细胞受体库的综合分析。利用免疫受体、RNA 和全外显子组测序，我们发现 B 细胞和 T 细胞反应似乎与转移性癌症基因组共同进化，并反映了肿瘤突变和新抗原结构。与转移性免疫监视和时间持久性相关的 B 细胞克隆更加扩展，并且与位点特异性克隆不同。 B 细胞克隆免疫监视和时间持续性可以从克隆结构中预测，中心性较高的 B 细胞抗原受体更有可能在多个转移灶或不同时间范围内被检测到。这种可预测性也适用于其他免疫介导的疾病。这项工作为优先考虑癌症治疗靶向的抗体序列奠定了基础。