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A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma

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 microenv...

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Main Authors: Andrade, Augusto Faria (Author) , Sigaud, Romain (Author) , Puligandla, Evan (Author) , Liu, Bridget (Author) , Karimi, Elham (Author) , Annett, Alva (Author) , Rezanejad, Morteza (Author) , Jawhar, Wajih (Author) , Taylor, Robert (Author) , Cao, Yi (Author) , Schmid, Simone (Author) , Selt, Florian (Author) , Hernáiz Driever, Pablo (Author) , Horn, Svea (Author) , Sievers, Philipp (Author) , Prinz, Marco (Author) , Glatzel, Markus (Author) , Mawrin, Christian (Author) , Hartmann, Christian (Author) , Monoranu, Camelia Maria (Author) , Konnikova, Liza (Author) , Sahm, Felix (Author) , Pfister, Stefan (Author) , Witt, Olaf (Author) , Jones, David T. W. (Author) , Koch, Arend Wolfgang (Author) , Kleinman, Claudia L. (Author) , Capper, David (Author) , Walsh, Logan (Author) , Jabado, Nada (Author) , Milde, Till (Author)
Format: Article (Journal)
Language:English
Published: 15 September 2025
In: Nature immunology
Year: 2025, Volume: 26, Issue: 10, Pages: 1794-1806, [16]
ISSN:1529-2916
DOI:10.1038/s41590-025-02268-7
Online Access:Resolving-System: https://dx.doi.org/10.1038/s41590-025-02268-7
Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41590-025-02268-7
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41590-025-02268-7
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Author Notes:Augusto Faria Andrade, Romain Sigaud, Evan Puligandla, Bridget Liu, Elham Karimi, Alva Annett, Morteza Rezanejad, Wajih Jawhar, Robert Taylor, Yi Cao, Simone Schmid, Florian Selt, Pablo Hernáiz Driever, Svea Horn, Philipp Sievers, Marco Prinz, Markus Glatzel, Christian Mawrin, Christian Hartmann, Camelia-Maria Monoranu, Liza Konnikova, Felix Sahm, Stefan M. Pfister, Olaf Witt, David T.W. Jones, Arend Koch, Claudia L. Kleinman, David Capper, Logan Walsh, Nada Jabado & Till Milde
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Summary: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.
Item Description:Gesehen am 03.02.2026
Physical Description:Online Resource
ISSN:1529-2916
DOI:10.1038/s41590-025-02268-7

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