Pediatric-Low--Grade-Gliomas Dataset

Pediatric low-grade gliomas (pLGG) are MAPK pathway-activated brain tumors prevalent inchildren and associated with significant morbidity despite favorable survival rates. Usingimaging mass cytometry, we spatially characterized at the single cell level the unexplored tumormicroenvironment (TME) across a large cohort of 120 pLGG cases, considering various factorslike age, molecular drivers, brain location, and tumor subtype. Our analysis revealed myeloidcells, comprising resident microglia and diverse bone marrow-derived macrophages, as thepredominant immune population in the TME, notably in optic pathway tumors, along withlimited T lymphoid infiltrates. In addition, we identified an immune signature that wasindependently predictive of progression-free survival. Spatial analysis unveiled specific cellularinteractions, including significant myeloid-myeloid interactions and macrophage-enrichedregions with MAPK-activated TIM3-expressing myeloid cells, suggesting animmunosuppressive TME. Our study, the largest on pLGG TME to date, offers a comprehensiveresource of the immune landscape of these tumors, and highlights the immunosuppressive role ofdiverse myeloid infiltrates, and suggests combining TIM-3 with MAPK inhibition as atherapeutic strategy to be functionally explored to target both the TME and oncogenic MAPKactivation in these brain tumors.