Interrogating immune niches in a murine GBM model under radiation therapy 3249

Description Adult glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with dismal median survival of only 14 months. Current standard of care treatment includes surgical resection followed by radiation therapy (RT) and temozolomide chemotherapy, a treatment regimen established in 2005. Our lab has developed an immune-competent, autochthonous adult GBM mouse model with expression of EGFRviii and PTEN/CDKN2a oncogene knockout. Using this model, we investigate immune composition in the tumor microenvironment (TME) and distal sites like the skull bone marrow, particularly in response to RT. We performed a single 8Gy dose of whole brain radiation and immune profiled 7 days later using immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics. Results showed reduced tumor burden in RT-treated groups and increased accumulation of IBA1+ macrophages in the TME. scRNA-seq revealed that brain-resident microglia and peripheral macrophages were the predominant immune cells. RT treatment led to an enrichment of CD49d+ peripheral macrophages and increased expression of Apoe and IL-1β, indicating a more pro-inflammatory phenotype. Additionally, RT induced changes in the myeloid and lymphoid cell populations in the skull bone marrow. Spatial transcriptomics of brain tissue is ongoing to map immune cell localization within the TME and surrounding tissue. This model provides insights into immune responses to therapeutic strategies in GBM. Funding Sources CIRM EDUC4-12751 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)