Diversification and shared features of tumor-binding antibody repertoires in tumor, sentinel lymph node, and blood of three patients with breast cancer. Homo sapiens

Several recent studies indicate that successful induction of B cell-mediated humoral immunity is associated with favorable clinical outcomes in cancer patients. While a considerable amount of data have been generated regarding phenotype and function of intra-tumoral B cells, an understanding of the intra-tumoral B cell repertoire in terms of anti-tumor specificity is not well understood. This study combined antibody phage display and specificity analysis with immune repertoire and transcriptional profiling of tumor and lymph node-associated B cells in three treatment-naive patients with breast cancer. Phage panning and binding studies against autologous tumors allowed us to identify tumor-binding antibodies from sentinel lymph nodes and tumor tissues. All three patients had detectable anti-tumor antibodies within the tumor compartment and the sentinel lymph node. B cell clonal lineage mapping across tissue libraries identified expanded clones present at multiple sites and revealed that some of these clones harbored extensive somatic hypermutation in both the tumor and the lymph node. These findings suggest that there is a chronic and evolving humoral immune response that targets the tumor. Studying the dynamics of tissue-based B-cell responses may provide personalized biomarkers such as tumor-associated B-cell clones for monitoring immunomodulatory therapies in patients with cancer.