P12.15.B Astrocyte immunometabolic regulation of the glioblastoma microenvironment drives tumor pathogenicity

Abstract Background Malignant brain tumors are the cause of a disproportionate level morbidity and mortality among cancer patients, an unfortunate statistic that has remained constant for decades. Despite considerable advances in molecular characterization these tumors, targeting cells yet to produce significant treatment. An alternative strategy is target glioblastoma microenvironment, such as tumor associated astrocytes. Astrocytes control multiple processes health disease, ranging from maintaining brain's metabolic homeostasis, modulating neuroinflammation. However, their role pathogenicity not well understood. Material Methods Immunocompetent mice were implanted with murine glioma cell lines astrocyte was analyzed, further investigated using in-vitro co-cultures. Results Here we report depletion reactive astrocytes regresses prolongs mouse survival. Analysis tumor-associated translatome, revealed initiate transcriptional programs shape immune compartments microenvironment. Specifically, expression CCL2 CSF1 governs recruitment macrophages promotes pro-tumorigenic macrophage phenotype. Concomitantly, demonstrate astrocyte-derived cholesterol key survival, astrocytic efflux, via ABCA1, halts progression. In summary, by reprogramming immunological properties microenvironment supporting non-oncogenic dependency on cholesterol. Conclusion These findings suggest immunometabolic signaling may help treat this uniformly lethal tumor.