Preclinical assessment of checkpoint blockade combined with DNA methyltransferase inhibition in high-risk pediatric brain tumors reveals limited therapeutic synergy.

ABSTRACT:

Abstract

BackgroundDespite intensive therapies, outcomes for high-risk pediatric brain tumors (PBTs) remain dismal, prompting the search for novel treatments. DNA methyltransferase inhibitors (DNMTi) have been shown to prime tumors to improve response to checkpoint inhibition. The aim of this study was to investigate the potential of decitabine (DAC), in combination with a PD-1 inhibitor, to improve survival in pediatric high-risk brain tumor models.

Methods

Analysis of human PBT datasets was performed to determine gene expression levels of immune cell markers. Tumor response to DAC, with or without a PD-1 inhibitor, was tested in murine models representing H3-wildtype diffuse intrinsic pontine glioma (DIPG), H3K27-mutant diffuse midline glioma (DMG), atypical teratoid rhabd

SUBMITTER: Mishra DK 

PROVIDER: S-EPMC12803780 | biostudies-literature | 2026 Jan-Dec

REPOSITORIES: biostudies-literature