CONICET | Buscador de Institutos y Recursos Humanos

Targeted disruption of lectin-glycan interactions promotes remodeling of tumor vascular networks and restores immune function. DO. Croci, JP. Cerliani, T. D´alotto, ID. Mascanfroni, M. Salatino, S. Mendez Huergo, LS. Dergan-Dylon and GA. Rabinovich. The mechanisms linking tumor neovascularization and immunity are poorly understood. We previously demonstrated an essential role of galectin-1 (Gal-1) in tumor-immune escape and angiogenesis. The present study was conducted to elucidate whether Gal1-glycan lattices can link tumor angiogenesis to immunity. We examined the ´glycophenotype´ of endothelial cells (ECs) in resting, proliferative, tolerogenic or inflammatory conditions. ECs exposed to tolerogenic or proliferative microenvironments exhibited a substantial up-regulation of cell surface glycans critical for Gal-1 binding (p<0.01). In vivo disruption of Gal1-glycan lattices in B16 melanomas attenuated hypoxia-driven angiogenesis, while promoting vascular remodeling (p<0.01) in tumors treated with anti-Gal1 blocking mAb. Moreover, anti-Gal1 treated tumors showed a significant reduction in tumor growth (p<0.01) and evoked a T-cell specific immune responses, as shown by increased infiltration of CD8+ T-cell (p<0.05), increased proliferation of tumor-specific CD4+ T-cells (p<0.01) and augmented IFN-g and IL-17 (p<0.05) production. Moreover, tumor-draining LN of mice receiving anti-Gal-1 mAb showed lower frequency of FoxP3+ Treg cells (p<0.05) and lower IL-10 secretion (p<0.05). Hence, disruption of lectin-glycan lattices, not only evokes an unleashed anti tumor immune response, but also favors remodeling of tumor vascular networks, highlighting the versatility of endogenous lectins during cancer progression.