TMIC-35. CROSSTALK BETWEEN TAMS AND GLIOBLASTOMA STEM-LIKE CELLS IN A HYPOXIC MICROENVIRONMENT INDUCES SENESCENCE ARREST AND ENHANCED RADIORESISTANCE

Abstract Patients with glioblastoma (GBM) have an overall survival of 15 months. These catastrophic rates are correlated systematic relapses that might arise from remaining stem cells (GSCs) left behind after treatments. Our goal was identifying whether radioresistance GBM is caused by GSCs and how hypoxia TAMs affect this process. First, we established a glioblastoma-brain cortical organoid (GBM-BCOs) to model human GBM. We co-cultured GFP-labeled neurosphere BCOs for 14 days observed tumor take rate 100% all tested. Next, evaluated enhanced migration into GBM-BCOs. incorporated THP-1 GFP-GBM-BCOS incubated 24 h under normoxic or hypoxic conditions. Hypoxia increased influx Further, investigated the enrichment in found that, co-culture GBM-BCOs system, CD133+ population 72 condition. In addition, IF tissue revealed IBA1+ peri-necrotic area compared non-necrotic tumor. To examine radioresistant phenotype quiescent population, irradiated grown conditions different doses γ-rays. After irradiation, these were MTT assay showed promoted increase markers (γ-H2AX IL-6) our exposure. results indicate, not only condition play key role radioresistance, but also crosstalk between promote oncogenesis contribute ineffective anti-tumor response.