ArticleCancer research2013
GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- Efficacy of vaccination therapy in newly diagnosed and recurrent glioblastoma patients: a meta-analysis.BMC cancer · 2025Pooled it
- Efficacy of anti-GD2 antibody immunotherapy with filgrastim and teceleukin versus standard treatment with sargramostim, aldesleukin and isotretinoin in children with high-risk neuroblastoma.International journal of clinical oncology · 2026Trial
- A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.Neuro-oncology · 2019Trial
- Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas.JCI insight · 2018Trial
- GM-CSF Promotes Neutrophil PD-L1 Expression Through the VEGFR-2/STAT6/CSF2 Signaling Axis in Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Myeloid-Derived Suppressor Cells: Function, Migration, and Therapeutic Opportunities in Glioblastoma.Cells · 2026Review
- Understanding the dual role of granulocyte-macrophage colony-stimulating factor in the lung cancer tumor microenvironment and its therapeutic implications.Translational lung cancer research · 2026Review
- Review
- Tumors located in the brain impair the frequency and phenotype of dendritic cells in blood and tumor.iScience · 2026Article
- [ACS omega · 2026Article
- 3D heterotypic models of glioblastoma reveal the impact of microglia on cellular organization and the production of a distinct secretome.Scientific reports · 2026Article
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- The paracrine effects of tumor cells on endothelial cells and macrophages in brain metastases with different primary sites.Frontiers in immunology · 2026Article
- Single-Nucleotide Polymorphisms Related to Glioblastoma Risk and Worldwide Epidemiology: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2025Review
- Coordinated changes in midkine expression and midkine-associated multiomic profile in glioma microenvironment.Scientific reports · 2025Article
- MARCO expression on myeloid-derived suppressor cells is essential for their differentiation and immunosuppression.Cell death discovery · 2025Article
- The Role of Viruses in the Glioma Tumor Microenvironment: Immunosuppressors or Primers for Anti-Tumor Immunity?Cancers · 2025Review
- CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy.The Journal of experimental medicine · 2025Article
- Glioma-neuronal circuit remodeling induces regional immunosuppression.Nature communications · 2025Article
- Functional 3D Human Neuron-Glioblastoma Model Reveals Cellular Interactions Enabling Drug Safety Assessments.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Malignant gliomas are lethal cancers in the brain and heavily infiltrated by myeloid cells. Interleukin-4 receptor-α (IL-4Rα) mediates the immunosuppressive functions of myeloid cells, and polymorphisms in the IL-4Rα gene are associated with altered glioma risk and prognosis. In this study, we sought to evaluate a hypothesized causal role for IL-4Rα and myeloid suppressor cells in glioma development. In both mouse de novo gliomas and human glioblastoma cases, IL-4Rα was upregulated on glioma-infiltrating myeloid cells but not in the periphery or in normal brain. Mice genetically deficient for IL-4Rα exhibited a slower growth of glioma associated with reduced production in the glioma microenvironment of arginase, a marker of myeloid suppressor cells, which is critical for their T-cell inhibitory function. Supporting this result, investigations using bone marrow-derived myeloid cells showed that IL-4Rα mediates IL-13-induced production of arginase. Furthermore, glioma-derived myeloid cells suppressed T-cell proliferation in an IL-4Rα-dependent manner, consistent with their identification as myeloid-derived suppressor cells (MDSC). Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a central role for the induction of IL-4Rα expression on myeloid cells, and we found that GM-CSF is upregulated in both human and mouse glioma microenvironments compared with normal brain or peripheral blood samples. Together, our findings establish a GM-CSF-induced mechanism of immunosuppression in the glioma microenvironment via upregulation of IL-4Rα on MDSCs.
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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.