IMMU-08. RAGE ABLATION ATTENUATES GLIOMA PROGRESSION AND ENHANCES TUMOR IMMUNE RESPONSES BY SUPPRESSING GALECTIN-3 EXPRESSION

Abstract INTRODUCTION Malignant gliomas consist of heterogenous cellular components that have adopted multiple overlapping escape mechanisms overcome both targeted and immune-based therapies. The receptor for advanced glycation end products (RAGE) is a member the immunoglobulin superfamily activated by diverse proinflammatory ligands present in tumor microenvironment (TME). Activation RAGE its stimulates signaling pathways are important growth, invasion, immune escape. OBJECTIVE We aimed to demonstrate blockade expression may tackle resistance inhibiting GBM progression, evasion. METHODS evaluated genetic ablation on tumorigenicity two syngeneic murine glioma models. was inhibited GL261 K-Luc shRNA CRSPR/Cas9 techniques prior intracranial implantation. Tumor inflammatory responses were examined immunohistochemistry, qPCR, ELISA, western blotting, NanoString, flow cytometry, vivo survival analysis. RESULTS Intracellular abrogated growth invasion suppressing AKT ERK1/2 activities downregulating MMP9 expression. Interestingly, inhibition also enhanced galectin-3, rendered immunotherapy resistant responsive checkpoint therapy, significantly increased survival. CONCLUSION This study first link with galactin-3 as an modulator glioblastoma revealed effect TME mediated through downregulation Gal-3 subsequent polarization Tumor-associated macrophages. therapeutic significance demonstrated sensitizing highly invasive immune-resistant model strongly supports development complementary treatment strategy malignant gliomas.