ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Neutrophils promote the malignant glioma phenotype through S100A4.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers, 1 of them a synthesis that pooled it.
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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
208 citing papers in PubMed, 1 synthesis or guideline pooled it, 281 citations in OpenAlex.
- Prognostic Significance of Preoperative Systemic Cellular Inflammatory Markers in Gliomas: A Systematic Review and Meta-Analysis.Clinical and translational science · 2020Pooled it
- Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients.Cancer immunology, immunotherapy : CII · 2019Trial
- The microenvironment of glioblastoma: in pursuit of universal multimodal immunotherapy.Acta neurologica Belgica · 2026Review
- Targeting the CMKLR1-Mediated Signaling Rebalances Immunometabolism State in Middle-Age Testicular Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neutrophils in glioblastoma: orchestrators of the tumor microenvironment and immune evasion.Molecular biology reports · 2026Review
- A prognostic matrix gene expression signature defines functional glioblastoma phenotypes and niches.Communications biology · 2026Article
- Influence of the Cholinergic System on the Pathogenesis of Glioblastoma: Impact of the Neutrophil Granulocytes.International journal of molecular sciences · 2025Article
- Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma.Nature communications · 2025Article
- Glioblastoma insights: Focus on crosstalk with the suppressive tumor microenvironment and advanced therapeutic strategies.Medicine · 2025Review
- Preoperative peripheral blood routine indicators as predictors of prognosis and diagnosis in glioma under the 2021 World Health Organization classification.Oncology letters · 2025Article
- In Vivo Behavior of Biomimetic Nanoparticles: Strategies for Clearance Avoidance, Targeting, and Functional Delivery.Molecules (Basel, Switzerland) · 2025Review
- S100A4 Induces Neutrophilic Inflammation in Chronic Rhinosinusitis with Nasal Polyps via TLR4 Pathway.Journal of clinical immunology · 2025Article
- Immunotherapy in central nervous system tumors.International journal of surgery (London, England) · 2025Review
- Article
- Single-cell dissection of the genotype-immunophenotype relationship in glioblastoma.Brain : a journal of neurology · 2025Article
- Tumor heterogeneity and resistance in glioblastoma: the role of stem cells.Apoptosis : an international journal on programmed cell death · 2025Review
- Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.Cancer communications (London, England) · 2025Review
- Immune factors and their role in tumor aggressiveness in glioblastoma: Atypical cadherin FAT1 as a promising target for combating immune evasion.Cellular & molecular biology letters · 2025Review
- Peripheral blood-derived immune cell counts as prognostic indicators and their relationship with DNA methylation subclasses in glioblastoma patients.Brain pathology (Zurich, Switzerland) · 2025Article
- Insights of immune cell heterogeneity, tumor-initiated subtype transformation, drug resistance, treatment and detecting technologies in glioma microenvironment.Journal of advanced research · 2025Review
148 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
purposeAntiangiogenic therapy is effective in blocking vascular permeability, inhibiting vascular proliferation, and slowing tumor growth, but studies in multiple cancer types have shown that tumors eventually acquire resistance to blockade of blood vessel growth. Currently, the mechanisms by which this resistance occurs are not well understood. EXPERIMENTAL
designIn this study, we evaluated the effects of neutrophils on glioma biology both in vitro and in vivo and determined target genes by which neutrophils promote the malignant glioma phenotype during anti-VEGF therapy.
resultsWe found that an increase in neutrophil infiltration into tumors is significantly correlated with glioma grade and in glioblastoma with acquired resistance to anti-VEGF therapy. Our data demonstrate that neutrophils and their condition media increased the proliferation rate of glioblastoma-initiating cells (GIC). In addition, neutrophils significantly increased GICs Transwell migration compared with controls. Consistent with this behavior, coculture with neutrophils promoted GICs to adopt morphologic and gene expression changes consistent with a mesenchymal signature. Neutrophil-promoting tumor progression could be blocked by S100A4 downregulation in vitro and in vivo. Furthermore, S100A4 depletion increased the effectiveness of anti-VEGF therapy in glioma.
conclusionsCollectively, these data suggest that increased recruitment of neutrophils during anti-VEGF therapy promotes glioma progression and may promote treatment resistance. Tumor progression with mesenchymal characteristics is partly mediated by S100A4, the expression of which is increased by neutrophil infiltration. Targeting granulocytes and S100A4 may be effective approaches to inhibit the glioma malignant phenotype and diminish antiangiogenic therapy resistance.
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What OpenQuestion holds
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.