%0 Journal Article
%A Andrade, Augusto Faria
%A Sigaud, Romain
%A Puligandla, Evan
%A Liu, Bridget
%A Karimi, Elham
%A Annett, Alva
%A Rezanejad, Morteza
%A Jawhar, Wajih
%A Taylor, Robert
%A Cao, Yi
%A Schmid, Simone
%A Selt, Florian
%A Hernáiz Driever, Pablo
%A Horn, Svea
%A Sievers, Philipp
%A Prinz, Marco
%A Glatzel, Markus
%A Mawrin, Christian
%A Hartmann, Christian
%A Monoranu, Camelia-Maria
%A Konnikova, Liza
%A Sahm, Felix
%A Pfister, Stefan
%A Witt, Olaf
%A Jones, David
%A Koch, Arend
%A Kleinman, Claudia L
%A Capper, David
%A Walsh, Logan
%A Jabado, Nada
%A Milde, Till
%T A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma.
%J Nature immunology
%V nn
%@ 1529-2908
%C London
%I Springer Nature Limited
%M DKFZ-2025-01917
%P nn
%D 2025
%Z #EA:B310#LA:B310# / epub
%X Pediatric low-grade gliomas (pLGGs) are mitogen-activated protein kinase (MAPK) pathway-activated brain tumors prevalent in children and are associated with morbidity despite favorable survival. Here using imaging mass cytometry, we spatially characterized at the single-cell level the tumor microenvironment (TME) of 120 pLGG cases, considering age, molecular drivers, brain location and tumor subtype. Our analysis identified myeloid cells-including resident microglia and bone marrow-derived macrophages-as the predominant immune population in the TME, particularly in optic pathway tumors. Additionally, we discovered an immune signature predictive of progression-free survival. Spatial analysis identified specific cellular interactions, notably myeloid-myeloid contacts and macrophage-enriched regions harboring MAPK-activated, TIM-3+ myeloid cells, suggesting an immunosuppressive TME. Our study provides a comprehensive resource on the immune landscape of these pLGGs and underscores the immunosuppressive role of diverse myeloid infiltrates. These findings also indicate that combining TIM-3 blockade with MAPK inhibition might be a promising therapeutic strategy to target both the TME and oncogenic MAPK activation in pLGG tumors.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40954250
%R 10.1038/s41590-025-02268-7
%U https://inrepo02.dkfz.de/record/304594