TY  - JOUR
AU  - Andrade, Augusto Faria
AU  - Sigaud, Romain
AU  - Puligandla, Evan
AU  - Liu, Bridget
AU  - Karimi, Elham
AU  - Annett, Alva
AU  - Rezanejad, Morteza
AU  - Jawhar, Wajih
AU  - Taylor, Robert
AU  - Cao, Yi
AU  - Schmid, Simone
AU  - Selt, Florian
AU  - Hernáiz Driever, Pablo
AU  - Horn, Svea
AU  - Sievers, Philipp
AU  - Prinz, Marco
AU  - Glatzel, Markus
AU  - Mawrin, Christian
AU  - Hartmann, Christian
AU  - Monoranu, Camelia-Maria
AU  - Konnikova, Liza
AU  - Sahm, Felix
AU  - Pfister, Stefan
AU  - Witt, Olaf
AU  - Jones, David
AU  - Koch, Arend
AU  - Kleinman, Claudia L
AU  - Capper, David
AU  - Walsh, Logan
AU  - Jabado, Nada
AU  - Milde, Till
TI  - A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma.
JO  - Nature immunology
VL  - nn
SN  - 1529-2908
CY  - London
PB  - Springer Nature Limited
M1  - DKFZ-2025-01917
SP  - nn
PY  - 2025
N1  - #EA:B310#LA:B310# / epub
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40954250
DO  - DOI:10.1038/s41590-025-02268-7
UR  - https://inrepo02.dkfz.de/record/304594
ER  -