Journal Article

DKFZ-2025-01917

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma.

Andrade, A. F. ; Sigaud, R. (First author)DKFZ* ; Puligandla, E. ; Liu, B. ; Karimi, E. ; Annett, A. ; Rezanejad, M. ; Jawhar, W. ; Taylor, R. ; Cao, Y. ; Schmid, S.DKFZ* ; Selt, F.DKFZ* ; Hernáiz Driever, P. ; Horn, S. ; Sievers, P.DKFZ* ; Prinz, M. ; Glatzel, M. ; Mawrin, C. ; Hartmann, C. ; Monoranu, C.-M. ; Konnikova, L. ; Sahm, F.DKFZ* ; Pfister, S.DKFZ* ; Witt, O.DKFZ* ; Jones, D.DKFZ* ; Koch, A. ; Kleinman, C. L. ; Capper, D.DKFZ* ; Walsh, L. ; Jabado, N. ; Milde, T. (Last author)DKFZ*

2025
Springer Nature Limited London

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Please use a persistent id in citations: doi:10.1038/s41590-025-02268-7

Abstract: 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.

Note: #EA:B310#LA:B310# / 2025 Oct;26(10):1794-1806

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Contributing Institute(s):

1. KKE Pädiatrische Onkologie (B310)
2. DKTK HD zentral (HD01)
3. DKTK Koordinierungsstelle Berlin (BE01)
4. KKE Neuropathologie (B300)
5. B062 Pädiatrische Neuroonkologie (B062)
6. Pädiatrische Gliomforschung (B360)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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