ArticleFrontiers in immunology2019
Progressive Impairment of NK Cell Cytotoxic Degranulation Is Associated With TGF-β1 Deregulation and Disease Progression in Pancreatic Cancer.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- IL-15 boosts mesothelin- and CD70-CAR NK cell potency in PDAC without added benefit from dual targeting.Molecular therapy. Oncology · 2026Article
- Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.Molecular cancer · 2026Article
- The natural killer-cellular humoral activation test as a functional biomarker of antibody-mediated rejection after kidney transplantation.Scientific reports · 2026Article
- Overcoming multidimensional immunotherapy resistance in PDAC: from microenvironment to clinic.Frontiers in immunology · 2026Review
- Oncogenic Potential of Epstein-Barr Virus in NK and NKT Cells Contribute to the Rapid Deterioration of Hemophagocytic Lymphohistiocytosis.Journal of medical virology · 2025Article
- Natural killer cells: the immune frontline against circulating tumor cells.Journal of experimental & clinical cancer research : CR · 2025Review
- Immune profiling of pediatric germ cell tumors identifies key cell populations and novel therapeutic targets.Frontiers in immunology · 2025Article
- HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Empowering pancreatic tumor homing with augmented anti-tumor potency of CXCR2-tethered CAR-NK cells.Molecular therapy. Oncology · 2024Article
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- The role of TGF-β in the tumor microenvironment of pancreatic cancer.Genes & diseases · 2023Review
- Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer.Scientific reports · 2023Article
- Microbiota Regulates Pancreatic Cancer Carcinogenesis through Altered Immune Response.Microorganisms · 2023Review
- p35 is a Crucial Player in NK-cell Cytotoxicity and TGFβ-mediated NK-cell Dysfunction.Cancer research communications · 2023Article
- Addressing Natural Killer Cell Dysfunction and Plasticity in Cell-Based Cancer Therapeutics.Cancers · 2023Review
- An integrated overview of the immunosuppression features in the tumor microenvironment of pancreatic cancer.Frontiers in immunology · 2023Review
- The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment.Frontiers in pharmacology · 2023Review
- Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients.Brain sciences · 2022Article
- A New Functional Screening Platform Identifies Colistin Sulfate as an Enhancer of Natural Killer Cell Cytotoxicity.Cancers · 2022Article
- Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are key effectors in cancer immunosurveillance and can be used as a prognostic biomarker in diverse cancers. Nonetheless, the role of NK cells in pancreatic cancer (PC) remains elusive, given conflicting data on their association with disease prognosis. In this study, using conventional K562 target cells and complementary engineered target cells providing defined and synergistic stimulation for NK cell activation, a correlation between impaired NK cell cytotoxic degranulation and PC progression was determined. Peripheral blood mononuclear cells (PBMCs) from 31 patients with newly diagnosed PC, 24 patients with non-malignant tumors, and 37 healthy controls were analyzed by flow cytometry. The frequency, phenotype, and effector functions of the NK cells were evaluated, and correlations between NK cell functions and disease stage and prognosis were analyzed. The results demonstrated that effector functions, but not frequency, of NK cells was progressively decreased on a per-cell basis during PC progression. Impaired cytotoxic degranulation, but not IFN-γ production, was associated with clinical features indicating disease progression, such as high serum CA19-9 and high-grade tumors. Significantly, this impairment correlated with cancer recurrence and mortality in a prospective analysis. Furthermore, the impaired cytotoxic degranulation was unrelated to NKG2D downregulation but was associated with increased circulating and tumor-associated TGF-β1 expression. Thus, NK cell cytotoxic activity was associated with PC progression and may be a favorable biomarker with predictive and prognostic value in PC.
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