ArticleBMC cancer2014
Elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates natural killer cell dysfunction.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 85 citations in OpenAlex.
- Dual roles of neutrophil extracellular traps in tumors: From pro-metastatic mechanisms to immunotherapeutic strategies (Review).Oncology letters · 2026Review
- Neutrophil extracellular traps in the tumor microenvironment, metastasis, therapy, and beyond: advances, challenges, and perspectives.Journal of hematology & oncology · 2026Review
- Review
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Neutrophil extracellular traps in tumor microenvironment for radiotherapy: friend or foe?Frontiers in immunology · 2026Review
- NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.Frontiers in immunology · 2026Review
- Neutrophil Plasticity and NETosis in Tumour Microenvironment: Tumour Evolution and Therapy Resistance.Journal of immunology research · 2026Review
- Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis.Acta pharmaceutica Sinica. B · 2025Review
- Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.Experimental hematology & oncology · 2025Review
- Inside a Metastatic Fracture: Molecular Bases and New Potential Therapeutic Targets.Cancer medicine · 2025Review
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Machine learning and gene network integration reveal prognostic subnetworks and biomarkers in pancreatic cancer.Computational and structural biotechnology journal · 2025Article
- Review
- GPR35-mediated metabolic reprogramming promotes tumorigenesis in digestive cancers.Frontiers in immunology · 2025Review
- Role of indoleamine 2, 3-dioxygenase 1 in immunosuppression of breast cancer.Cancer pathogenesis and therapy · 2024Review
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- The Role of Tumor Microenvironment in Pancreatic Cancer Immunotherapy: Current Status and Future Perspectives.International journal of molecular sciences · 2024Review
- Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- Suppression of the antitumoral activity of natural killer cells under indirect coculture with cancer-associated fibroblasts in a pancreatic TIME-on-chip model.Cancer cell international · 2023Article
- Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma.Molecular cancer · 2023Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNatural killer (NK) cells play a key role in non-specific immune response in different cancers, including pancreatic cancer. However the anti-tumor effect of NK cells decreases during pancreatic cancer progression. The regulatory pathways by which NK cells facilitate tumor immune escape are unclear, therefore our purpose was to investigate the roles of the contributory factors.
methodsNK cells isolated from fresh healthy peripheral blood were co-cultured with normal human pancreatic ductal cells hTERT-HPNE and human pancreatic cancer cell lines SW1990 and BxPc-3 in vitro. Then NK cell function was determined by Flow cytometric analysis of surface receptors and cytotoxic granules in NK cells, NK cell apoptosis and cytotoxicity, and Enzyme-linked immunosorbent assay of cytokines. Expression level of MMP-9, IDO and COX-2 in hTERT-HPNE and SW1990 cells were detected by quantitative RT-PCR. Statistical differences between data groups were determined by independent t-tests using SPSS 19.0 software.
resultsOur results showed that NK cell function was significantly downregulated following exposure to pancreatic cancer cells compared to normal pancreatic cells, as demonstrated by lower expressions of activating surface receptors (NKG2D, DNAM-1, NKp30 and NKp46) and cytotoxic granules (Perforin and Granzyme B); decreased secretion of cytokines (TNF-α and IFN-γ); and reduced cytotoxicity against myelogenous leukemia K562 cells. Further investigations revealed that MMP-9 and IDO may be implicated in SW1990 cell-induced NK cell dysfunction by facilitating tumor immune evasion. Blockade by TIMP-1 and/or 1-MT could partially restore NK function.
conclusionsTaken together, elevation of MMP-9 and IDO induced by pancreatic cancer cells mediates NK cell dysfunction. Our findings could contribute to the development of NK cell-based immunotherapy in patients with pancreatic cancer.
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Registered trials
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