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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.
摘要：
B细胞和T细胞是适应性免疫系统的重要组成部分，并介导抗癌免疫。癌症中的T细胞景观是很好的特征，但是B细胞对抗癌免疫监视的贡献还没有得到很好的研究。在这里，我们显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。使用免疫受体，RNA和全外显子组测序，我们发现B细胞和T细胞反应似乎都与转移性癌症基因组共同进化，并反映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。从克隆结构可以预测B细胞克隆免疫监视和时间持久性，具有较高中心性的B细胞抗原受体，更有可能在多个转移或跨时间检测到。这种可预测性在其他免疫介导的疾病中是可推广的。这项工作为优先考虑用于癌症治疗靶向的抗体序列奠定了基础。
