Human Granulocytic Myeloid-Derived Suppressor Cells (G-Mdscs) in Metastatic Breast Cancer Patients is a Heterogeneous Population with Angiogenic Potential in Vivo.
CANCER IMMUNOLOGY RESEARCH(2020)
摘要
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 Rydén, 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.
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