Kyra Boorsma Bergerud

Meningiomas are the most common tumors of the central nervous system. Treatment of meningioma, consisting of surgical resection followed by radiation therapy (RT), can be compromised by the activity of immunosuppressive cells in the tumor microenvironment (TME). Previous research identified populations of immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in meningioma tissue. While radiation therapy (RT) is critical to efficacious treatment, RT can embolden immunosuppressive interactions in the TME. Preliminary studies in mice suggest that ablative RT and conventionally fractionated RT may exert different biological effects on the immune system. This study sought to classify the impact of a dose of ablative vs. conventionally fractionated RT on immunosuppressive cell activity in meningioma. A benign, NF2-mutant meningioma was collected after surgical resection and dissociated. Primary cell cultures were irradiated at doses of 0 Gy, 2 Gy, and 15 Gy and incubated at 37 degrees in 5% CO2 for 18 hours before staining. Cell populations were analyzed using flow cytometry within one week of staining. MDSCs, defined as CD11b⁺CD33⁺HLA-DR^-, were minimal across all RT groups. Comparatively, a large population of CD11b⁺CD33⁺CD14⁺ cells with high HLA-DR expression was identified. The frequency of these cells was highest at the 2 Gy dose and lowest at the 15 Gy dose. In contrast, intracellular expression of TGF-ꞵ, IFN-γ, and IL-10 among this subpopulation increased with RT dose. These data may suggest that conventionally fractionated vs. ablative RT doses may differentially stimulate immunosuppressive macrophages in meningioma.