ArticleBrain : a journal of neurology2021
Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade glioma.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Myeloid compartment reprogramming through nanoparticle-delivered resiquimod blocks paracrine growth support and activates phagocytosis to slow tumor progression in endogenous mouse medulloblastoma and diffuse midline glioma models.bioRxiv : the preprint server for biology · 2026Article
- Therapeutic efficacy of dendritic cell vaccination in a novel syngeneic mouse model of diffuse hemispheric glioma, H3 G34-mutant.Journal of neuro-oncology · 2026Article
- Microglial GPR35 Ameliorates Epileptogenesis and Neuroinflammation via PDGFA Domain 2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models.The Journal of clinical investigation · 2026Article
- Stabilization of RUNX1 Induced by O-GlcNAcylation Promotes PDGF-BB-Mediated Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancer research · 2025Article
- IL13RA2-integrated genetically engineered mouse model allows for CAR T cells targeting pediatric high-grade gliomas.Acta neuropathologica communications · 2025Article
- The Complexity of Malignant Glioma Treatment.Cancers · 2025Review
- Gold and Silver Nanoparticles Efficiently Modulate the Crosstalk Between Macrophages and Cancer Cells.International journal of nanomedicine · 2025Article
- Immunosuppressive Microenvironment in H3K27 Mutant Pediatric Diffuse Midline Glioma: Single-Cell and Bioinformatics Insights on CD8A, IL7R, and ICAM1.Current medicinal chemistry · 2025Article
- Cytokine profile of cerebrospinal fluid in pediatric patients with metastatic medulloblastoma.Heliyon · 2024Article
- Article
- Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function.Nature communications · 2024Article
- Review
- H3K27M mutant glioma: Disease definition and biological underpinnings.Neuro-oncology · 2024Review
- PDGFBB facilitates tumorigenesis and malignancy of lung adenocarcinoma associated with PI3K-AKT/MAPK signaling.Scientific reports · 2024Article
- Review
- Myeloid cells as potential targets for immunotherapy in pediatric gliomas.Frontiers in pediatrics · 2024Review
- Natural plant-derived polysaccharides targeting macrophage polarization: a promising strategy for cancer immunotherapy.Frontiers in immunology · 2024Review
- Targeting diffuse midline gliomas: The promise of focused ultrasound-mediated blood-brain barrier opening.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Paediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12-15 months. One promising avenue of research is the development of novel therapies targeting the properties of non-neoplastic cell-types within the tumour such as tumour associated macrophages (TAMs). TAMs are immunosuppressive and promote tumour malignancy in adult HGG; however, in paediatric medulloblastoma, TAMs exhibit anti-tumour properties. Much is known about TAMs in adult HGG, yet little is known about them in the paediatric setting. This raises the question of whether paediatric HGGs possess a distinct constituency of TAMs because of their unique genetic landscapes. Using human paediatric HGG tissue samples and murine models of paediatric HGG, we demonstrate diffuse midline gliomas possess a greater inflammatory gene expression profile compared to hemispheric paediatric HGGs. We also show despite possessing sparse T-cell infiltration, human paediatric HGGs possess high infiltration of IBA1+ TAMs. CD31, PDGFRβ, and PDGFB all strongly correlate with IBA1+ TAM infiltration. To investigate the TAM population, we used the RCAS/tv-a system to recapitulate paediatric HGG in newborn immunocompetent mice. Tumours are induced in Nestin-positive brain cells by PDGFA or PDGFB overexpression with Cdkn2a or Tp53 co-mutations. Tumours driven by PDGFB have a significantly lower median survival compared to PDGFA-driven tumours and have increased TAM infiltration. NanoString and quantitative PCR analysis indicates PDGFB-driven tumours have a highly inflammatory microenvironment characterized by high chemokine expression. In vitro bone marrow-derived monocyte and microglial cultures demonstrate bone marrow-derived monocytes are most responsible for the production of inflammatory signals in the tumour microenvironment in response to PDGFB stimulation. Lastly, using knockout mice deficient for individual chemokines, we demonstrate the feasibility of reducing TAM infiltration and prolonging survival in both PDGFA and PDGFB-driven tumours. We identify CCL3 as a potential key chemokine in these processes in both humans and mice. Together, these studies provide evidence for the potent inflammatory effects PDGFB has in paediatric HGGs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.