ArticleMolecular cancer2013
Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses 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
113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Global trends in tumor-associated neutrophil research: a bibliometric and visual analysis.Frontiers in immunology · 2025Pooled it
- Tumor-associated neutrophils suppress CD8British journal of cancer · 2024Pooled it
- Clinical and prognostic value of neutrophil-lymphocyte ratio for patients with thyroid cancer: A meta-analysis.Medicine · 2020Pooled it
- Repurposing of the Macrolide Antibiotic Clarithromycin for the Prevention of Lung Cancer.Molecular cancer therapeutics · 2026Article
- Neutrophils in non-small cell lung cancer and immunotherapy with PD-1/PD-L1 inhibitors.Journal of translational medicine · 2025Review
- Targeting tumor-associated neutrophils: A promising strategy in lung cancer immunotherapy.Cancer pathogenesis and therapy · 2025Review
- Targeting neutrophils for cancer therapy.Nature reviews. Drug discovery · 2025Review
- Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025Review
- Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity.Signal transduction and targeted therapy · 2025Review
- Neutrophil extracellular traps in tumor metabolism and microenvironment.Biomarker research · 2025Review
- The miR-941/FOXN4/TGF-β feedback loop induces N2 polarization of neutrophils and enhances tumor progression of lung adenocarcinoma.Frontiers in immunology · 2025Article
- Chemokines and their receptors in the esophageal carcinoma tumor microenvironment: key factors for metastasis and progression.Frontiers in oncology · 2025Review
- Neutrophil-and-monocyte-to-lymphocyte ratio is positively associated with elevated prostate-specific antigen levels and high-risk prostate cancer: evidence from the NHANES (2003-2008).Frontiers in cell and developmental biology · 2025Article
- Article
- A key regulator of tumor-associated neutrophils: the CXCR2 chemokine receptor.Journal of molecular histology · 2024Review
- Immune Cell Migration to Cancer.Cells · 2024Review
- Unconventional strategy could be the future: From target to KRAS broad range treatment.Heliyon · 2024Review
- Targeting neutrophil elastase is a promising direction for future cancer treatment.Discover oncology · 2024Review
- Immunologic tumor microenvironment modulators for turning cold tumors hot.Cancer communications (London, England) · 2024Review
- Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2024Review
53 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
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTumor cells produce various cytokines and chemokines that attract leukocytes. Leukocytes can amplify parenchymal innate immune responses, and have been shown to contribute to tumor promotion. Neutrophils are among the first cells to arrive at sites of inflammation, and the increased number of tumor-associated neutrophils is linked to poorer outcome in patients with lung cancer.
resultsWe have previously shown that COPD-like airway inflammation promotes lung cancer in a K-ras mutant mouse model of lung cancer (CC-LR). This was associated with severe lung neutrophilic influx due to the increased level of neutrophil chemoattractant, KC. To further study the role of neutrophils in lung tumorigenesis, we depleted neutrophils in CC-LR mice using an anti-neutrophil antibody. This resulted in a significant reduction in lung tumor number. We further selectively inhibited the main receptor for neutrophil chemo-attractant KC, CXCR2. Similarly, this resulted in suppression of neutrophil recruitment into the lung of CC-LR mice followed by significant tumor reduction. Neutrophil elastase (NE) is a potent elastolytic enzyme produced by neutrophils at the site of inflammation. We crossed the CC-LR mice with NE knock-out mice, and found that lack of NE significantly inhibits lung cancer development. These were associated with significant reduction in tumor cell proliferation and angiogenesis.
conclusionWe conclude that lung cancer promotion by inflammation is partly mediated by activation of the IL-8/CXCR2 pathway and subsequent recruitment of neutrophils and release of neutrophil elastase. This provides a baseline for future clinical trials using the IL-8/CXCR2 pathway or NE inhibitors in patients with lung cancer.
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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.