TMIC-08. FRIEND AND FOE: RADIATION THERAPY MODULATES GLIOBLASTOMA IMMUNE EVASION VIA EXTRACELLULAR VESICLES

Abstract

Abstract Glioblastoma (GBM) is the most common form of malignant primary brain tumor and despite optimal treatment, long-term survival remains incredibly rare. Radiation therapy (RT) leads to successful initial tumor regression but recurrence is inevitable. Previous studies have shown that ionizing radiation changes the composition of the tumor microenvironment and alters the expression of immune-related markers on tumor cells. Extracellular vesicles (EVs) are vesicular bodies of cellular origin and secreted by nearly every cell. They have been shown to carry a variety of cargo (DNA, proteins, RNAs, lipids) which can be taken up by other cells. Notably, previous studies highlight that EVs drive GBM progression and immune evasion by acting as multifunctional signaling complexes. Here we show that ionizing radiation of GBM cells results in an altered EV secretome and further facilitates the uptake of EVs in recipient cells. In addition, EVs secreted by GBM cells following radiation modulate the tumor microenvironment by manipulating the innate as well as the adaptive immune response. Macrophages exposed to EVs from irradiated GBM cells switched to the tumor supportive M2 phenotype and exhibited decreased phagocytotic ability.We dissected a novel mechanism by which GBM evades the immune system with the help of EVs following RT, pointing towards novel therapeutic strategies to prevent GB recurrence.