Reprogramming the immune suppressive tumor microenvironment in glioma enhances the efficacy of immune-mediated gene therapy - PubMed
2 hours ago
- #tumor microenvironment
- #CD73 blockade
- #glioma immunotherapy
- Mutant IDH1 gliomas exhibit reduced CD73 expression and adenosine levels due to DNA hypermethylation, contributing to an immune-permissive TME.
- Wild-type IDH1 gliomas have high CD73 expression, making CD73 a potential immunotherapy target, but monotherapy blockade did not improve survival in mouse models.
- Combining CD73 inhibition with Ad-TK/Ad-Flt3L immune-stimulatory gene therapy enhanced efficacy and increased anti-glioma T cell activity in wtIDH1 glioma-bearing mice.
- The study suggests CD73 inhibition combined with Ad-TK/Ad-Flt3L gene therapy could be an effective treatment for wtIDH1 gliomas, with potential for clinical translation.