Investigating the role and regulation of B cells in Triple Negative Breast Cancer Liver Metastasis 3428

Abstract Description Metastasis is the leading cause of cancer deaths, with liver metastases in up to 60% of Triple Negative Breast Cancer (TNBC) cases contributing to the lowest survival rates among metastatic patients. In TNBC mouse models sensitive to immune-based therapy, B cells are essential for improved survival and prognostic of TNBC patient survival. Despite these data, the field has yet to understand the role and regulation of B cells in breast cancer liver metastasis. To overcome the limitations that the metastasis field currently faces regarding representative models, we have created a novel mouse model of TNBC-LM. Using this innovative tool, we have begun to characterize changes in the tumor microenvironment of the primary breast tumor, tumor draining lymph node, and metastatic liver associated with specific B cell phenotypes. Single-cell RNA sequencing data and confocal microscopy reveal changes in B cell subsets, clonal dynamics, and organization across tissue types and cancerous conditions. Longitudinal flow cytometry data describes changes in adaptive lymphocyte dynamics and status throughout metastatic progression. We hypothesize that TNBC cells can metastasize to the liver by disabling B cell activity through tolerance mechanisms and establishing an immune-suppressive tumor microenvironment. Understanding the mechanisms governing anti-metastatic B cell activity will inform development of therapeutics for metastasis; an urgently needed area given the poor prognosis for patients. Funding Sources Supported by T32GM133351 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)