RBIO-19. Radiation-Mediated MDSC Immunodynamics in Recurrent High-Grade Glioma

Abstract Myeloid-derived suppressor cells (MDSCs) contribute to an immunosuppressive tumor microenvironment that facilitates cancer progression, particularly in patients with high-grade gliomas. We previously reported that increased MDSCs during chemoradiotherapy (chemoRT) is associated with poor outcomes. This study investigates the effect of radiotherapy on immune checkpoint expression on MDSC subsets in patients with recurrent high-grade glioma receiving a second course of RT. Peripheral blood samples were collected on the first and last day of RT. Peripheral blood mononuclear cells (PBMCs) were isolated and subsequently stained with immunofluorescent antibodies to identify and analyze MDSC subsets (HLA-DR, CD33, CD14, CD15) and expression of checkpoint molecules (TIM-3, TIGIT, PD-1, PD-L1, CTLA-4) by flow cytometry. Because MDSCs secrete TGF-β1 and it is a potent immune cell regulator, plasma TGF-β1 concentration was quantified using ELISA in both recurrent and naïve glioma patients. A Kolmogorov-Smirnov assessed normality while paired T-test was used to compare groups, with significance set at p<0.05. Five of 20 and 19 of 25 planned patients have enrolled in our IRB-approved PBMC and plasma protocols at the University of Minnesota Medical Center, respectively. Increased frequency of total MDSCs (12.8%;p< 0.05) and the monocytic(m)-MDSC subset (10.8%;p< 0.05) was measured. Within the total MDSC and mMDSC populations, increased PD-L1 (14.5%, 18.8%, respectively;p< 0.05)) TIM-3 (23.6%, 18.0%, respectively) expression was measured after reirradiation. Increased plasma TGF-β1 was measured in patients with recurrent glioma (+0.143 fold change) compared to patients with naïve glioma (-0.300 fold change) after RT (p<0.05). Preliminary data supports that radiation may negatively influence systemic MDSC-associated immunosuppressive signaling, particularly with recurrent disease. Further understanding of immunodynamic changes secondary to RT will inform personalized immunotherapy strategies for patients with recurrent high-grade glioma.