Gliomas are incurable malignancies notable for having an immunosuppressive microenvironment with abundant myeloid cells, the immunomodulatory phenotypes of which remain poorly defined1. Here we systematically investigate these phenotypes by integrating single-cell RNA sequencing, chromatin accessibility, spatial transcriptomics and glioma organoid explant systems. We discovered four immunomodulatory expression programs: microglial inflammatory and scavenger immunosuppressive programs, which are both unique to primary brain tumours, and systemic inflammatory and complement immunosuppressive programs, which are also expressed by non-brain tumours. The programs are not contingent on myeloid cell type, developmental origin or tumour mutational state, but instead are driven by microenvironmental cues, including tumour hypoxia, interleukin-1β, TGFβ and standard-of-care dexamethasone treatment. Their relative expression can predict immunotherapy response and overall survival. By associating t

Erez et al. adapt single-molecule technologies to decode histone modification patterns on plasma-circulating nucleosomes from the blood of patients with pediatric high-grade glioma. They further devel...