Targeted disruption of lectin-glycan interactions promotes remodeling of tumor vascular networks and restores immune function. (P2173)

Abstract

Abstract 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-γ 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.