H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Diffuse Hemispheric Gliomas.

ABSTRACT: Diffuse hemispheric glioma (DHG), H3 G34-mutant, representing 9-15% of cases, are aggressive Central Nervous System (CNS) tumors with poor prognosis. This study examines the role of epigenetic reprogramming of the immune microenvironment and the response to immune-mediated therapies in G34-mutant DHG. To this end, we utilized human G34-mutant DHG biopsies, primary G34-mutant DHG cultures, and genetically engineered G34-mutant mouse models (GEMMs). Our findings show that the G34 mutation alters histone marks' deposition at promoter and enhancer regions, leading to the activation of the JAK/STAT pathway, which in turn results in an immune-permissive tumor microenvironment. The implementation of Ad-TK/Ad-Flt3L immunostimulatory gene therapy significantly improved median survival, and lead to

SUBMITTER: Garcia-Fabiani MB 

PROVIDER: S-EPMC10312611 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature