The priming of glioblastoma with a burst of radiation increased dramatically the uptake of extracellular vesicles-based immunotherapy by the tumor and the surrounding microenvironment, halting tumor growth, inducing anti-tumor immunity, and prolonging survival in animal models. In glioblastomas primed with radiation, extracellular vesicles allowed the immunotherapy to cross the blood-brain barrier, recruiting immune cells to the tumor site and reversing the expression of PD-L1, the protein responsible for immunosuppression of the larger tumor environment.