EZH2 inhibition and 5-azacytidine enhance antitumor immunity in PTEN-deficient glioblastoma by activation viral mimicry response.

ABSTRACT:

Background

PTEN-deficient glioblastoma (GBM) is characterized by an immunosuppressive tumor microenvironment (TME), therapeutic resistance, and poor prognosis. Emerging evidence suggests that dysregulation of the endogenous retrovirus (ERV)-MAVS-IFN pathway may contribute to immune evasion in cancer, but its role in PTEN-deficient GBM remains unclear.

Methods

Using flow cytometry and single-cell RNA sequencing, we analyzed the immune landscape of PTEN-deficient GBM. We evaluated the effects of 5-azacytidine (5-AZA) monotherapy and its combination with EZH2 inhibition (EZH2i) on ERV reactivation, type I interferon (IFN) responses, and TME remodeling. Mechanistic studies focused on H3K27me3-mediated epigenetic regulation of ERV expression.

Results

We found that PTEN def

SUBMITTER: Zhu D 

PROVIDER: S-EPMC12164629 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature