TMIC-47. SINGLE-CELL TRANSCRIPTOMICS REVEALS ANTITUMOR IMMUNE RESPONSES OF PROTON TREATMENT IN GLIOBLASTOMA

Abstract Proton therapy is an innovative radiation modality that has been shown to induce higher cytotoxicity tumor cells compared standard x-ray while sparing normal tissue. However, the impact of proton radiotherapy on growth and progression glioblastoma (GBM) not defined. We hypothesize understanding evolution micro environmental responses critical for developing targeting interventions. In this study, we investigate effect versus photon microenvironment in orthotopic syngeneic GBM model over course treatment. characterized tissues at early, progressing, terminal phases post irradiation by single cell transcriptomics, bulk RNA sequencing, histology. find led a drastic reduction volume early stages before eventual recurrence. treatment exhibits equivalent if superior, control when radiation. Single transcriptomics analyses show dramatic increase immune populations including T macrophage which peak shortly addition, identify exhausted markers such as PD1, Tim-3, Lag-3 irradiation. Treatment with therapeutic agents reprogram microglia/macrophages anti-tumor phenotype activate effector functions effectively eradicate recurrence Thus, our study demonstrates powerful combined strategy against provides valuable information about how respond therapies, well potential mechanisms response GBM.