GLYCOSYLATION-DEPENDENT CIRCUITS SYNCHRONIZE THE PRO-ANGIOGENIC AND IMMUNOREGULATORY FUNCTIONS OF MYELOID-DERIVED SUPPRESSOR CELLS IN CANCER

BLIDNER, ADA G.; BACH, CAMILA; GARCÍA, PABLO A.; CAGNONI, ALEJANDRO J.; MANSELLE-COCCO, MONTANA N.; PINTO, NICOLÁS; TORRES, NICOLAS; GATTO, SABRINA G.; SARRIAS, LUCIANA; GIRIBALDI, MARÍA LAURA; MERLO, JOAQUÍN P.; PEREZ SAEZ, JUAN MANUEL; SALATINO, MARIANA; TRONCOSO, MARÍA F.; MARIÑO, KARINA V.; ABBA, MARTÍN C.; CROCI, DIEGO O.; RABINOVICH, GABRIEL A.

Virtual

Congreso; Reunion de Biociencias 2021; 2021

SAIC, SAI

Myeloid-derived suppressor cells (MDSCs) favor tumor progression and therapy resistance by reprogramming antitumor immunity and promoting angiogenesis. To elucidate the mechanisms that synchronize these functions, we investigated the role of glycosylation-dependent, galectin-1 (Gal1)-driven circuits in coupling immunoregulatoryand pro-angiogenic activities of MDSCs. Flow cytometry and HPLC-HILIC/WAX revealed an activation-dependent glycan profile 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 angiogenesis programs in bone marrow derived MDSCs. Flow cytometry of Gal1-conditioned MDSCs showed higher expression of immune checkpoint molecules, including programmeddeath ligand-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