626 Targeting a novel carbohydrate that serves as an immune checkpoint and angiogenic regulator for treatment of melanoma

Abstract

We discovered DC-HIL/Gpnmb receptor expressed by melanoma and myeloid-derived suppressor cells (MDSC), with 2 functions, immune checkpoint and angiogenesis, both mediated by its binding to syndecan-4 (SD4) on activated T cells and select endothelial cells (EC), respectively. Using microarray technology, we now report that DC-HIL’s precise ligand on SD4 is a rare heparan sulfate (rHS) saccharide sulfated highly at positions 2-O/6-O. Consistently with this discovery, HS sulfotransferases required for rHS synthesis rises markedly during T-cell activation, and knocking-down gene expression by specific shRNA abrogated DC-HIL binding to T cells/EC.