ArticleInternational journal of molecular sciences2023
Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Metabolic Control of Immunity-Unveiling Neutrophil Mechanisms.Advances in experimental medicine and biology · 2026Review
- Tumor-associated neutrophils in pancreatic ductal adenocarcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Uncovering common transcriptional features shared by mature peripheral blood PMN-MDSCs and tumor-infiltrating neutrophils in humans.Oncoimmunology · 2025Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Tumor-derived exosomes induce neutrophil infiltration and reprogramming to promote T-cell exhaustion in hepatocellular carcinoma.Theranostics · 2025Article
- Prognostic heterogeneity of Ki67 in non-small cell lung cancer: A comprehensive reappraisal on immunohistochemistry and transcriptional data.Journal of cellular and molecular medicine · 2024Article
- Identification of fibronectin type III domain containing 3B as a potential prognostic and therapeutic target for pancreatic cancer: a preliminary analysis.European journal of medical research · 2024Article
- Emerging roles of MITF as a crucial regulator of immunity.Experimental & molecular medicine · 2024Review
- Harnessing glucose metabolism with nanomedicine for cancer treatment.Theranostics · 2024Review
- Imaging glucose metabolism to reveal tumor progression.Frontiers in physiology · 2023Review
- Ze-qi Decoction Inhibits Neutrophil Extracellular Trap Formation to Suppress the Progression and Metastasis of Non-Small Cell Lung Cancer.Integrative cancer therapiesArticle
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Large numbers of neutrophils infiltrate tumors and comprise a notable component of the inflammatory tumor microenvironment. While it is established that tumor cells exhibit the Warburg effect for energy production, the contribution of the neutrophil metabolic state to tumorigenesis is unknown. Here, we investigated whether neutrophil infiltration and metabolic status promotes tumor progression in an orthotopic mouse model of pancreatic ductal adenocarcinoma (PDAC). We observed a large increase in the proportion of neutrophils in the blood and tumor upon orthotopic transplantation. Intriguingly, these tumor-infiltrating neutrophils up-regulated glycolytic factors and hypoxia-inducible factor 1-alpha (HIF-1α) expression compared to neutrophils from the bone marrow and blood of the same mouse. This enhanced glycolytic signature was also observed in human PDAC tissue samples. Strikingly, neutrophil-specific deletion of HIF-1α (HIF-1αΔNφ) significantly reduced tumor burden and improved overall survival in orthotopic transplanted mice, by converting the pro-tumorigenic neutrophil phenotype to an anti-tumorigenic phenotype. This outcome was associated with elevated reactive oxygen species production and activated natural killer cells and CD8+ cytotoxic T cells compared to littermate control mice. These data suggest a role for HIF-1α in neutrophil metabolism, which could be exploited as a target for metabolic modulation in cancer.
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