Combined inhibition of FACT and BET disrupts transcription to suppress tumor growth in mouse models of diffuse midline glioma

; and alterations to the splicing landscape. This combination also elicited immune-related effects, including activation of the interferon response and antigen presentation mechanisms in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting with spatial transcriptomics. Together, our data highlight the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor.