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

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

Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencias 2021; 2021

SAIC, SAI, SAFIS

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 immunoregulatory and 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 DSCs showed higher expression of immune 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