ArticleThe Journal of clinical investigation2020
Relief of tumor hypoxia unleashes the tumoricidal potential of neutrophils.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Global trends in tumor-associated neutrophil research: a bibliometric and visual analysis.Frontiers in immunology · 2025Pooled it
- Single-cell transcriptomic unveils tumor-mediated reprogramming of neutrophils and their unique vulnerability that inhibits metastasis.Science advances · 2026Article
- Persistent Gene Activation as a Molecular Signature of Ulcerative Colitis Progression to Colorectal Cancer.Digestive diseases and sciences · 2026Article
- Metabolic adaptations of immunosuppressive cells in cancer: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- Hijacking emergency granulopoiesis: Neutrophil ontogeny and reprogramming in cancer.Molecular oncology · 2026Review
- Single-Cell and Multiomic Analysis Reveals Neutrophil Heterogeneity and Prognostic Value in Cervical Lesions.Cancer science · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- New insights into the tumor immune microenvironment and immunotherapy of thyroid cancer.Frontiers in immunology · 2026Review
- Regulatory role of phosphatidylcholine metabolic reprogramming in colorectal cancer progression and neutrophil interactions.iScience · 2025Article
- Hypoxia-induced EGR1 remodels neutrophils to suppress antitumor immunity.Science immunology · 2025Article
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Clinical significance of systemic inflammation response index and platelet-lymphocyte ratio in patients with stage I-III gastric cancer.World journal of gastrointestinal surgery · 2025Article
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Single-cell transcriptome analysis identifies MIF as a novel tumor-associated neutrophil marker for pancreatic ductal adenocarcinoma.NPJ precision oncology · 2025Article
- Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025Review
- Neutrophil Dynamics in Response to Cancer Therapies.Cancers · 2025Review
- Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.Cancer communications (London, England) · 2025Review
- Tumor-associated neutrophils and neutrophil extracellular traps in lung cancer: antitumor/protumor insights and therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Single-cell and spatial transcriptomics reveals an anti-tumor neutrophil subgroup in microwave thermochemotherapy-treated lip cancer.International journal of oral science · 2025Article
29 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
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Polymorphonuclear neutrophils (PMNs) are increasingly recognized to influence solid tumor development, but why their effects are so context dependent and even frequently divergent remains poorly understood. Using an autochthonous mouse model of uterine cancer and the administration of respiratory hyperoxia as a means to improve tumor oxygenation, we provide in vivo evidence that hypoxia is a potent determinant of tumor-associated PMN phenotypes and direct PMN-tumor cell interactions. Upon relief of tumor hypoxia, PMNs were recruited less intensely to the tumor-bearing uterus, but the recruited cells much more effectively killed tumor cells, an activity our data moreover suggested was mediated via their production of NADPH oxidase-derived reactive oxygen species and MMP-9. Simultaneously, their ability to promote tumor cell proliferation, which appeared to be mediated via their production of neutrophil elastase, was rendered less effective. Relieving tumor hypoxia thus greatly improved net PMN-dependent tumor control, leading to a massive reduction in tumor burden. Remarkably, this outcome was T cell independent. Together, these findings identify key hypoxia-regulated molecular mechanisms through which PMNs directly induce tumor cell death and proliferation in vivo and suggest that the contrasting properties of PMNs in different tumor settings may in part reflect the effects of hypoxia on direct PMN-tumor cell interactions.
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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.