ArticleJournal of translational medicine2015
Favorable in vitro effects of combined IL-12 and IL-18 treatment on NK cell cytotoxicity and CD25 receptor expression in metastatic melanoma patients.
Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Surface-Engineered Natural Killer Cell-Derived Small Extracellular Vesicles Induce Potent Anti-Tumour Effects in Lung Cancer Cells.Journal of extracellular biology · 2025Article
- Interleukin-12 in multimodal tumor therapies for induction of anti-tumor immunity.Discover oncology · 2024Review
- Demonstrating the immunostimulatory and cytokine-augmentation effects of bacterial ghosts on natural killer cells and Caenorhabditis Elegans.Biotechnology and bioengineering · 2024Article
- Article
- The Role of IL-18 in P2RX7-Mediated Antitumor Immunity.International journal of molecular sciences · 2023Review
- CD25Oncoimmunology · 2023Article
- Inhibition of MC38 colon cancer growth by multicomponent chemoimmunotherapy with anti-IL-10R antibodies, HES-MTX nanoconjugate, depends on application of IL-12, IL-15 or IL-18 secreting dendritic cell vaccines.Frontiers in immunology · 2023Article
- Antitumor Activities of Interleukin-12 in Melanoma.Cancers · 2022Review
- Review
- The Beneficial Effect of IL-12 and IL-18 Transduced Dendritic Cells Stimulated with Tumor Antigens on Generation of an Antitumor Response in a Mouse Colon Carcinoma Model.Journal of immunology research · 2022Article
- SIRT2 promotes murine melanoma progression through natural killer cell inhibition.Scientific reports · 2021Article
- SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway.Cells · 2020Article
- Effect of interleukins (IL-2, IL-15, IL-18) on receptors activation and cytotoxic activity of natural killer cells in breast cancer cell.African health sciences · 2020Article
- Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Exploration of surface glycoprotein to design multi-epitope vaccine for the prevention of Covid-19.Informatics in medicine unlocked · 2020Article
- Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types.Frontiers in immunology · 2020Review
- Interleukin-18 Is a Prognostic Biomarker Correlated with CD8Journal of clinical medicine · 2019Article
- Key features and homing properties of NK cells in the liver are shaped by activated iNKT cells.Scientific reports · 2019Article
- Immune Suppression Mediated by STAT4 Deficiency Promotes Lymphatic Metastasis in HNSCC.Frontiers in immunology · 2019Article
- Non-Genetically Improving the Natural Cytotoxicity of Natural Killer (NK) Cells.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs IL-12 and IL-18 have important immunostimulatory role the aim of this study was to investigate their in vitro effects on functional and receptor characteristics of NK cells and their subsets in healthy controls (HC) and metastatic melanoma patients (MM).
methodsPeripheral blood mononuclear cells (PBMC) of HC and MM were stimulated with culture medium alone, medium supplemented with IL-12 (10 ng/ml), IL-18 (100 ng/ml) and their combination. NK cell activity was determined using radioactive cytotoxicity assay, while perforin, CD107a and pSTAT-4 expression, IFN-γ production and the expression of NKG2D, DNAM-1, CD161, CD158a/b, CD25, IL-12R beta 1/2 receptors on CD3(-)CD56(+) NK cells and their CD3(-)CD56(dim+) and CD3(-)CD56(bright+) subsets were analyzed by flow cytometry. Cytokine induced level of DAP10 in PBMC was analyzed by reverse transcription polymerase chain reaction.
resultsIL-12 alone or in combination with IL-18 significantly induced NK cell activity and CD107a degranulation marker expression in MM and HC, while IL-18 alone did not have any effect in patients. The combination of IL-12 and IL-18 significantly increased mean fluorescence intensity (MFI) of IFN-γ in all NK cell subsets in HC and only in the bright subset in MM. MM that belong to M1c group with metastasis in liver and increased LDH serum values had significantly lower increase in NK cell cytotoxicity after combined IL-12 and IL-18 treatment compared to the patients in M1a and M1b categories. These results could be explained by decreased IL-12R expression and lower increase in pSTAT-4 and perforin expression in NK cells of M1c patients after IL-12 and combined IL-12 and IL-18 treatment. IL-18 alone significantly decreased NKG2D receptor expression and level of DAP10 signaling molecule in MM, while combined IL-12 and IL-18 increased the expression of CD25 on all NK cell subsets in HC and MM. Additionally, MM that belong to M1a + M1b group had significantly higher increase in CD25 receptor expression compared to the patients in M1c group.
conclusionsThe novel data obtained in this study support the use of IL-12 and IL-18 in combination for developing new therapeutic strategies for metastatic melanoma especially for patients with better survival rate and prognosis.
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