ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017
IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. 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, 69 citations in OpenAlex.
- An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer.Cancer control : journal of the Moffitt Cancer CenterTrial
- Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy.International journal of oral science · 2025Review
- The Practical Landscape of Cytokine-Targeted miRNAs to Enhance NK Cell Function in Cancer Immunotherapy: A Bioinformatic Analysis.Cancer reports (Hoboken, N.J.) · 2025Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Advances in the role of NK cells in MDS immune dysfunction and antitumor research.Frontiers in immunology · 2025Review
- Based on the immune system: the role of the IL-2 family in pancreatic disease.Frontiers in immunology · 2025Review
- Targeting protein modification: a new direction for immunotherapy of pancreatic cancer.International journal of biological sciences · 2025Review
- From bench to bedside: the past, present and future of IL-21 immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- NK cell-based tumor immunotherapy.Bioactive materials · 2024Review
- Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.International journal of biological sciences · 2024Review
- Therapeutic potential of interleukin-21 in cancer.Frontiers in immunology · 2024Review
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- The application of Interleukin-2 family cytokines in tumor immunotherapy research.Frontiers in immunology · 2023Review
- Advances and Prospects in the Treatment of Pancreatic Cancer.International journal of nanomedicine · 2023Review
- Identification of MYEOV-Associated Gene Network as a Potential Therapeutic Target in Pancreatic Cancer.Cancers · 2022Article
- Natural killer cells in antitumour adoptive cell immunotherapy.Nature reviews. Cancer · 2022Review
- The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?Biomedicines · 2022Review
- Theranostic potential of self-luminescent branched polyethyleneimine-coated superparamagnetic iron oxide nanoparticles.Beilstein journal of nanotechnology · 2022Article
- Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer.Frontiers in immunology · 2022Review
- Application of natural killer cells in pancreatic cancer.Oncology letters · 2021Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAlternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status. EXPERIMENTAL
designNK cells from normal donors or donors with pancreatic cancer were used to assess ADCC, IFN-γ release, and T-cell chemotaxis toward human pancreatic cancer cell lines. The in vivo efficacy of IL-21 in combination with cetuximab was evaluated in a subcutaneous and intraperitoneal model of pancreatic cancer.
resultsNK cell lysis of cetuximab-coated wild-type and mutant kras pancreatic cancer cell lines were significantly higher following NK cell IL-21 treatment. In response to cetuximab-coated pancreatic tumor cells, IL-21-treated NK cells secreted significantly higher levels of IFN-γ and chemokines, increased chemotaxis of T cells, and enhanced NK cell signal transduction via activation of ERK and STAT1. Treatment of mice bearing subcutaneous or intraperitoneal EGFR-positive pancreatic tumor xenografts with mIL-21 and cetuximab led to significant inhibition of tumor growth, a result further enhanced by the addition of gemcitabine.
conclusionsThese results suggest that cetuximab treatment in combination with IL-21 adjuvant therapy in patients with EGFR-positive pancreatic cancer results in significant NK cell activation, irrespective of KRAS mutation status, and may be a potential therapeutic strategy. Clin Cancer Res; 23(2); 489-502. ©2016 AACR.
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