ArticleCellular & molecular immunology2017
Human fused NKG2D-IL-15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells.
Article in Cellular & molecular immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- The Neuroimmune Axis in Gastric Cancer: Bridging Neural Regulation, Tumor Microenvironment, and Immunotherapy.Oncology research · 2026Review
- Genetic variants ofFrontiers in immunology · 2026Article
- HIF-1α: A Key Factor Mediating Tumor Cells from Digestive System to Evade NK Cell Killing via Activating Metalloproteinases to Hydrolyze MICA/B.Biomolecules · 2025Review
- Clinical significance of the tumor microenvironment on immune tolerance in gastric cancer.Frontiers in immunology · 2025Review
- Article
- Cancer immunity by tissue-resident type 1 innate lymphoid cells and killer innate-like T cells.Immunological reviews · 2024Review
- Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.International journal of biological sciences · 2024Review
- Review
- Immunology and immunotherapy in gastric cancer.Clinical and experimental medicine · 2023Review
- Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice.Frontiers in immunology · 2023Article
- Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.Trends in immunology · 2022Review
- Review
- The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?Biomedicines · 2022Review
- Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer.Frontiers in immunology · 2022Review
- microRNA-144/451 decreases dendritic cell bioactivityFrontiers in immunology · 2022Article
- IL-15-induced lymphocytes as adjuvant cellular immunotherapy for gastric cancer.Investigational new drugs · 2021Article
- 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
- Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy.Signal transduction and targeted therapy · 2020Review
- Review
- Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis.International journal of molecular sciences · 2020Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin (IL)-15 plays an important role in natural killer (NK) and CD8+ T-cell proliferation and function and is more effective than IL-2 for tumor immunotherapy. The trans-presentation of IL-15 by neighboring cells is more effective for NK cell activation than its soluble IL-15. In this study, the fusion protein dsNKG2D-IL-15, which consisted of two identical extracellular domains of human NKG2D coupled to human IL-15 via a linker, was engineered in Escherichia coli. DsNKG2D-IL-15 could efficiently bind to major histocompatibility complex class I chain-related protein A (MICA) of human tumor cells with the two NKG2D domains and trans-present IL-15 to NK or CD8+ T cells. We transplanted human gastric cancer (SGC-7901) cells into nude mice and mouse melanoma cells with ectopic expression of MICA (B16BL6-MICA) into C57BL/6 mice. Then, we studied the anti-tumor effects mediated by dsNKG2D-IL-15 in the two xenografted tumor models. Human dsNKG2D-IL-15 exhibited higher efficiency than IL-15 in suppressing gastric cancer growth. Exogenous human dsNKG2D-IL-15 was centrally distributed in the mouse tumor tissues based on in vivo live imaging. The frequencies of human CD56+ cells infiltrated into the tumor tissues following the injection of peripheral blood mononuclear cells into nude mice bearing human gastric cancer were significantly increased by human dsNKG2D-IL-15 treatment. Human dsNKG2D-IL-15 also delayed the growth of transplanted melanoma (B16BL6-MICA) by activating and recruiting mouse NK and CD8+ T cells. The anti-melanoma effect of human dsNKG2D-IL-15 in C57BL/6 mice was mostly decreased by the in vivo depletion of mouse NK cells. These data highlight the potential use of human dsNKG2D-IL-15 for tumor therapy.Cellular & Molecular Immunology advance online publication, 14 September 2015; doi:10.1038/cmi.2015.81.
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