Galectin-1 Reinforces The Immunosupressive Activity Of Extracllular Vesicles Released By Myeloid-Derived Suppressor Cells

BACH CA; MERLO JP; PERROTTA RM; SCHEIDEGGER MA; CHAURIO R; NAGY MZ; MANSELLE-COCCO, MN.; CONEJO GARCÍA JR; BLIDNER, AG.; RABINOVICH, GA.

Congreso; Reunion Anual de Biociencias 2022; 2022

Myeloid-Derived Suppressor Cells (MDSCs) represent a major hurdle for cancer immunotherapy by blunting antitumor T cell responses. Emerging evidence suggests that extracellular vesicles (EVs) shedding serves as an MDSC immunosuppression mechanism; however, the molecular mediators that trigger this effect are still elusive. We have recently demonstrated that Galectin-1 (Gal1), a b-galactoside-binding protein, enhances the MDSC immunosuppressive and pro-angiogenic activities of MDSCs. Here, we investigated the role of Gal1 in the biology of MDSC EVs. We differentiated MDSCs from mouse bone marrow in vitro, incubated them with recombinant Gal1, and isolated EVs released (control EVs or Gal1 EVs). We characterized EVs by imaging flow cytometry, transmission electron microscopy, cytokine array, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic analysis. Regarding tetraspanins, well-established EV markers, CD9 but not CD63 or CD81 were detected on the surface of MDSC EVs, as evidenced by imaging flow cytometry and LC-MS/MS. Interestingly, Gal1 EVs displayed lower levels of CD206 compared to control EVs. LC-MS/MS showed differential modulation of proteins in control EVs vs. Gal1 EVs. The glycosylation signature of MDSC EVs was assessed by flow cytometry revealing higher levels of asialo-core-1-O-glycans, leading to higher Gal1 binding on Gal1 EVs compared to control EVs (p