ArticleCancer immunology, immunotherapy : CII2018
Anergic natural killer cells educated by tumor cells are associated with a poor prognosis in patients with advanced pancreatic ductal adenocarcinoma.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Prognostic Significance of Tumor-Infiltrating Natural Killer Cells in Solid Tumors: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2020Pooled it
- Skeletal Muscle Index, Tumor and Systemic Immunity, and Survival in Advanced Pancreatic Ductal Adenocarcinoma.Cancer medicine · 2026Article
- Effective allogeneic natural killer cell therapy for pancreatic adenocarcinoma avails conserved activating receptors and evades HLA I-driven inhibition.Journal for immunotherapy of cancer · 2026Article
- The diversity of natural killer cell functional and phenotypic states in cancer.Cancer metastasis reviews · 2025Review
- Innate immune cell barrier-related genes inform precision prognosis in pancreatic cancer.Frontiers in immunology · 2025Article
- Clinical multi-dimensional prognostic nomogram for predicting the efficacy of immunotherapy in NSCLC.Scientific reports · 2024Article
- Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- Hsa-miR-301a-3p inhibited the killing effect of natural killer cells on non-small cell lung cancer cells by regulating RUNX3.Cancer biomarkers : section A of Disease markers · 2023Article
- Review
- Article
- Advances in NK cell production.Cellular & molecular immunology · 2022Review
- Natural killer cells in pancreatic cancer stroma.World journal of gastroenterology · 2021Review
- Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Analysis of N6-Methyladenosine Modification Patterns and Tumor Immune Microenvironment in Pancreatic Adenocarcinoma.Frontiers in genetics · 2021Article
- Pancreatic Adenocarcinoma Invasiveness and the Tumor Microenvironment: From Biology to Clinical Trials.Biomedicines · 2020Review
- Natural killer cells in cancer biology and therapy.Molecular cancer · 2020Review
- Absolute Counts of Peripheral Lymphocyte Subsets Correlate with the Progression-Free Survival and Metastatic Status of Pancreatic Neuroendocrine Tumour Patients.Cancer management and research · 2020Article
- Anergic natural killer cells educated by tumor cells are associated with a poor prognosis in patients with advanced pancreatic ductal adenocarcinoma.Cancer immunology, immunotherapy : CII · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
introductionNatural killer cells (NK) are often believed to play a positive role in the antitumor immune response. However, this is not the case for patients with advanced pancreatic cancer. This study was performed to determine the unique subtype of "educated" NK cells and their prognostic value in patients with advanced pancreatic cancer.
methodsWe divided 378 eligible patients into a derivation cohort (September 2010 to December 2014, n = 239) and a validation cohort (January 2015 to April 2016, n = 139). Flow cytometry was performed to analyze NK cells. Enzyme-linked immunosorbent assay was used to detect interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. The Kaplan-Meier method and the Cox proportional hazards model were used.
resultsSurvival analysis showed that a high density of NK cells accompanied by a high neutrophil-to-lymphocyte ratio was associated with reduced overall survival in both the derivation and validation cohorts. Multivariable analysis also showed that high NK infiltration (HR 1.45, 95% CI 1.17 to 1.79, p = 0.001) was an independent prognostic factor. In these patients, high NK infiltration was associated with reduced levels of IL-2, IFN-γ and TNF-α, although only IFN-γ reached statistical significance, which accounted for this unique phenomenon. DISCUSSION: Natural killer cells in patients with advanced pancreatic cancer are a unique subtype with anergic features. A high density of NKs predicts poor survival in these patients, possibly because an active inflammatory response and reduced secretion of IL-2, IFN-γ and TNF-α inhibit NK activation.
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Registered trials
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