Abstract A73: Human granulocytic myeloid-derived suppressor cells (G-MDSCs) in metastatic breast cancer patients is a heterogeneous population with angiogenic potential in vivo

MDSCs are potent immunosuppressive myeloid cells that have been implicated in various diseases, including cancer. In humans, MDSCs are divided into Mo-GMDSCs and G-MDSCs subgroups, depending on their surface phenotype and function. While their immunosuppressive properties have been extensively studied, knowledge about their origin and their tumor-promoting functions per se remains scarce. In this study, we demonstrate that G-MDSCs are significantly enriched in the peripheral blood of locoregional recurrent metastatic breast cancer (LRR/MBC) compared to healthy donors. The G-MDSCs display a heterogeneous population with a morphology representing one blast-like and one polymorphonuclear (PMN) population. In a breast cancer xenograft model, co-transplanting G-MDSCs sorted from LRR/MBC together with breast cancer cells significantly promoted angiogenesis and tumor growth. Gene expression profiling analysis revealed that G-MDSCs from LRR/MBC rather clustered with neutrophils from healthy donors, sharing similar expression in genes relevant for angiogenesis, lymphangiogenesis and immunosuppression, but surprisingly not with G-MDSCs from sepsis patients. We conclude that enrichment of G-MDSCs in metastatic breast cancer represents a heterogeneous population of activated neutrophils that can promote angiogenesis and tumor progression, and immature blasts of yet unknown character. Citation Format: Meliha Mehmeti, Caroline Bergenfelz, Daniel Bexell, Robert Carlsson, Rebecka Hellsten, Anna-Maria Larsson, Niklas Loman, Kristian Riesbeck, Jonas Ahl, Camilla Rydberg-Millrud, Gesine Paul-Visse, Lisa Ryden, Fredrika Killander, Karin Leandersson. Human granulocytic myeloid-derived suppressor cells (G-MDSCs) in metastatic breast cancer patients is a heterogeneous population with angiogenic potential in vivo [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A73.