TBIO-07. SINGLE-CELL TRANSCRIPTOMIC PROFILE REVEALS MACROPHAGE HETEROGENEITY IN SONIC-HEDGEHOG MEDULLOBLASTOMA AND THEIR DISTINCT RESPONSES TO DIFFERENT TREATMENT MODALITIES

Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment. Pro-inflammatory macrophages can suppress while anti-inflammatory macrophages can promote tumor growth. Despite their abundance in many tumors, the origins and diversity of TAMs are not well understood, especially in pediatric brain tumors. Using single-cell RNA sequencing in a genetically engineered mouse model (Ptch+/-:p53-/-) of SHH-MB, we identified the dual microglia and monocytic origin of macrophage and their transcriptomic heterogeneity. We demonstrate differential recruitment and function of macrophages under distinct modalities of tumor therapy of molecular targeted hedgehog inhibition versus radiation. We additionally identify a monocytic macrophage population recruited post-radiation that is immune suppressive, suggesting a mechanism for radiation treatment failure. These insights uncover potential strategies for immunomodulation as adjunctive therapy for radiation.