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<p>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<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月15日

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  • 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

摘要

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.