RBIO-10. RADIATION FRACTION SIZE DIFFERENTIALLY AFFECTS MYELOID-DERIVED SUPPRESSOR CELL (MDSC) SUBSETS IN WHO GRADE 1 MENINGIOMA

Abstract Meningiomas are often cured after focal therapy with surgical resection and/or radiotherapy (RT); however, a small proportion still recur. RT dose can be used to modulate anti-tumor immune responses, potentially through regulating immunosuppressive MDSCs. Here, we investigate the effect of a single fraction of RT (2Gy vs. 15Gy) on frequency and activation status of MDSC subsets in patients with WHO grade 1 meningioma. We hypothesize that 2Gy will promote immunosuppressive MDSC activity more than 15Gy. Fresh tumor cells from patients with a presumed diagnosis of meningioma were digested into primary cell cultures and treated with a single fraction of 2 or 15 Gy or were sham irradiated using a XRAD 320 Biological Irradiator. Cells were incubated for 18hrs prior to flow cytometric analysis. MDSC populations were identified as Live/Dead-CD11b+CD33+HLA-DR-. MDSC subsets were then divided into M-MDSC (CD14+CD15-) or G-MDSC (CD15+CD14-). Five WHO grade 1 meningiomas were analyzed. The total frequency of MDSCs in tumors increased from 3% with sham RT to 4% after irradiation with 2Gy (p=0.03). This was driven by a 2-fold increase in frequency of total M-MDSCs, as G-MDSCs decreased by half after 2Gy (p=0.03). After irradiation with 15Gy, M-MDSC frequency was nearly half that of 2Gy. The frequency of TGF-β+MDSCs increased after 15 Gy (p=0.02). The frequency of IL-10+G-MDSCs increased in response to 2Gy (p =0.03) but decreased 4-fold after 15Gy. 18hrs after 2Gy, IFN-γ+M-MDSCs increased compared to sham (p=0.01). In this small cohort of grade 1 meningiomas, a 2Gy fraction of RT appeared to support expansion of the M-MDSC subset. RT at both fraction sizes increased immunosuppressive cytokine producing-MDSCs: M-MDSC-IL-10; G-MDSC-TGF-β. These findings indicate the need for further studies to understand the subset-specific impact of RT on MDSC, a key immune cell type in brain cancers.