FRIEND AND FOE: RADIATION THERAPY INCREASES GLIOBLASTOMA IMMUNE EVASION VIA EVS

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor and despite optimal treatment, long-term survival is extremely rare. Radiation therapy (RT) leads to successful initial tumor regression but recurrence is inevitable. Previous studies have shown that ionizing radiation leads to a change of immune-related markers on tumor cells. Extracellular vesicles (EVs) are membranous structures secreted by nearly every cell and have been shown drive GBM progression by acting as multifunctional signaling complexes. Here, we show that radiation of GBM cells leads to an altered EV secretion/uptake dynamic, composition, and protein content. Furthermore, we show that EVs secreted by radiated GBM cells modulate the innate (microglia/macrophages) as well as adaptive (T-cells) immune response in the tumor microenvironment. We dissected a novel mechanism by which GBM evades the immune system via EVs following RT, pointing towards novel therapeutic strategies to prevent GBM recurrence.