Dr. Castro and colleagues show that mutant IDH1 epigenetically suppresses CD73 expression, limiting adenosine production and reprogramming the glioma microenvironment toward immune permissiveness. This work has been accepted for publication in Cell Press – Molecular Therapy Oncology (In Press). CD73 inhibition in wild-type IDH1 glioma models enhances the efficacy of immune-stimulatory gene therapy, revealing a mechanistically grounded combinatorial strategy to overcome immunosuppression and improve therapeutic responses.