Evento
Glycosylation-dependent circuits synchronize the pro-angiogenic and immunoregulatory functions of myeloid-derived suppressor cells in cancer
Blidner, Ada Gabriela
; Bach, Camila Agustina
; García, Pablo Alfredo
; Cagnoni, Alejandro
; Manselle Cocco, Montana Nicolle
; Pinto, Nicolás Alejandro
; Torres, Nicolás
; Gatto, Sabrina Gisela
; Sarrias, Luciana; Giribaldi, María Laura
; Merlo, Joaquín Pedro
; Pérez Sáez, Juan Manuel
; Salatino, Mariana
; Troncoso, María Fernanda
; Mariño, Karina Valeria
; Abba, Martín Carlos
; Croci, Diego O.; Rabinovich, Gabriel Adrián
Tipo del evento:
Reunión
Nombre del evento:
LXVI Annual Meeting of Sociedad Argentina de Investigación Clínica; LXIX Annual Meeting of Sociedad Argentina de Inmunología; LIII Annual Meeting of Asociación Argentina de Farmacología Experimental and XI Annual Meeting of Asociación Argentina de Nanomedicinas
Fecha del evento:
17/11/2021
Institución Organizadora:
Sociedad Argentina de Investigación Clínica;
Sociedad Argentina de Inmunología;
Asociación Argentina de Farmacología Experimental;
Asociación Argentina de Nanomedicina;
Título de la revista:
Medicina (Buenos Aires)
Editorial:
Fundación Revista Medicina
Idioma:
Inglés
Clasificación temática:
Resumen
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<0.05). In vivo, Gal1-conditionedMDSCs accelerated tumor growth (p=0.001) and fosteredimmune evasion and vascularization programs in Gal1-deficient colorectal tumors. Mechanistically, mass spectrometry,immunoblot and blocking assays identified the CD18/CD11b/CD177 complex as a bona fide Gal1 receptor and STAT3 asa key signaling pathway coupling these functions. Accordingly, a combined algorithm that integrates Gal1 expressionand MDSC phenotype, showed critical prognostic value bydelineating the immune landscape and clinical outcome ofhuman cancers. Thus, glycosylation-dependent Gal1-drivencircuits favor tumor progression by coupling immunoregulatory and pro-angiogenic programs of MDSCs via CD18- andSTAT3-dependent pathways.
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Eventos(IBYME)
Eventos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Eventos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Eventos(IHEM)
Eventos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Eventos de INST. HISTOLOGIA Y EMBRIOLOGIA DE MEND DR.M.BURGOS
Eventos(IMEX)
Eventos de INST.DE MEDICINA EXPERIMENTAL
Eventos de INST.DE MEDICINA EXPERIMENTAL
Eventos(IQUIFIB)
Eventos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Eventos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Glycosylation-dependent circuits synchronize the pro-angiogenic and immunoregulatory functions of myeloid-derived suppressor cells in cancer; LXVI Annual Meeting of Sociedad Argentina de Investigación Clínica; LXIX Annual Meeting of Sociedad Argentina de Inmunología; LIII Annual Meeting of Asociación Argentina de Farmacología Experimental and XI Annual Meeting of Asociación Argentina de Nanomedicinas; Argentina; 2021; 75-75
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