Reprogramming the Immune Suppressive Tumor Microenvironment in Glioma Enhances the Efficacy of Immune-Mediated Gene Therapy

Many CNS WHO grade 2–3 and some grade 4 gliomas harbor mutant isocitrate dehydrogenase 1 (mIDH1), which causes a gain of function mutation (IDH1 R132H) leading to the production of 2-hydroxyglutarate (2HG). Mutant IDH1-induced 2HG, through epigenetic reprogramming elicits an immune-permissive tumor microenvironment (TME).

An immunosuppressive mechanism in the glioma TME involves adenosine production via the ectoenzyme CD73. This study investigates mIDH1’s influence on CD73 expression and adenosine levels. We demonstrate that mIDH1 glioma cells exhibit reduced CD73 expression, driven by DNA hypermethylation, leading to reduced adenosine levels.