SYST-32 A NOVEL APPROACH TO TARGET TREG-MEDIATED IMMUNOSUPPRESSION IN GBM

Abstract Macrophage inflammatory protein-3, or MIP-3α, is a chemokine that highly expressed in gliomas, with expression progressively increasing tumor grade. It one of the top genes pseudopalisading and perinecrotic zones glioblastoma (GBM) as chemokine, can greatly influence tumor-immune interactions. The receptor for CCR6, found on variety GBM-infiltrating immune subsets such γδ T cells, conventional CD4 cells most notably, Tregs, which disproportionately increased GBM patients. Patients lower CCR6-MIP3α gene signatures tumors have improved overall survival disease-free progression. We circulating MIP-3α also presence intracranial glioma mice, be normalized immunotherapy. note ablation CCR6 remarkably improves response glioma-bearing mice to anti-PD-1 therapy. Mechanistically, we observed reduction regulatory cell immunosuppressive phenotype ablation, CD8 effector function against cells. Specifically, marks glycolytic known mechanism immunosuppression from Tregs reduces their capacity immunosuppressivity. Targeting CCR6:MIP-3α axis therefore promising approach alleviate improve anti-tumor response.