Glycosylation-dependent circuits synchronize the pro-angiogenic and immunoregulatory functions of myeloid-derived suppressor cells in cancer

Myeloid-derived suppressor cells (MDSCs) favor tumorprogression and therapy resistance by reprogramming antitumor immunity and promoting angiogenesis. To elucidatethe mechanisms that synchronize these functions, we investigated the role of glycosylation-dependent, galectin-1(Gal1)-driven circuits in coupling immunoregulatory andpro-angiogenic activities of MDSCs. Flow cytometry andHPLC-HILIC/WAX revealed an activation-dependent glycanprofile in monocytic and polymorphonuclear MDSCs (p=0.03)that controlled Gal1 binding and was more prominent in tumor microenvironments. Exposure to Gal1 led to concomitant activation of immunosuppression and angiogenesisprograms in bone marrow derived MDSCs. Flow cytometryof Gal1-conditioned MDSCs showed higher expression ofimmune checkpoint molecules, including programmed deathligand-1 (PD-L1) (p=0.005) and indoleamine 2,3-dioxygenase (IDO) (p=0.037) and greater production of reactive oxygen species (ROS) and nitric oxide (NO) (p=0.02). In vitro,Gal1-conditioned MDSCs showed greater T-cell suppressive capacity (p=0.03) and higher IL-10 (p=0.04) and IL-27(p=0.003) secretion. These effects were accompanied by enhanced endothelial cell migration, tube formation, 3D-sprouting and vascularization (p