Adipocytes upregulate immunosuppressive mechanisms on triple negative breast cancer cells 3744

Abstract Description Triple negative breast cancer (TNBC) represents 15% of all breast cancer incidence and accounts for 40% of all breast cancer-related mortality, having the highest mortality of all breast cancer subtypes. Despite our increasing understanding of how obesity promotes TNBC progression, mechanistic insight into this relationship, including knowledge of therapeutically targetable drivers of this disease, is limited. Published studies from our lab have demonstrated that obesity-induced Galectin-9 (GAL-9), which has immunosuppressive properties, is a driver of B-cell acute lymphoblastic leukemia. Similarly, culturing human TNBC cells lines in the adipocyte secretome significantly upregulated the gene and surface expression of this lectin after 24, 48 and 72 hours of culture determined by qPCR and flow cytometry, respectively. Furthermore, using flow cytometry, I have found that the adipocyte secretome significantly upregulates the surface expression of Programmed death ligand 2 (PD-L2) on TNBC cell lines. The 2021 approval of pembrolizumab, an antibody inhibitor of programmed death ligand pathways, was approved for high-risk, early-stage, TNBC; however, its currently unknown if the efficacy is altered in patients with obesity. Overall, my data suggests that adipocytes directly upregulate multiple immunosuppressive mechanisms in TNBC cells and studies are warranted to determine how antibody-mediated inhibition of the GAL-9 and PD-1 pathways impacts the elimination of cancer cells. Funding Sources NIH; THE PATTEN DAVIS FOUNDATION; THE CU ANSCHUTZ SOM DEAN DIVERSITY FUNDING; CU CANCER CENTER PILOT FUNDING; THE GATES FOUNDATION (CU ANSCHUTZ) Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)