ArticlePloS one2014
IL-12 directs further maturation of ex vivo differentiated NK cells with improved therapeutic potential.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
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- Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond.International journal of molecular sciences · 2022Review
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- Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era.Breast (Edinburgh, Scotland) · 2021Review
- Implications of a 'Third Signal' in NK Cells.Cells · 2021Review
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- Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy.Cells · 2020Review
- Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy.Frontiers in cell and developmental biology · 2020Review
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- On the Way to Become a Natural Killer Cell.Frontiers in immunology · 2019Review
- Cancer treatment and the KIR-HLA system: an overview.Clinical and experimental medicine · 2017Review
- Bortezomib augments lymphocyte stimulatory cytokine signaling in the tumor microenvironment to sustain CD8+T cell antitumor function.Oncotarget · 2017Article
- Developmental and Functional Control of Natural Killer Cells by Cytokines.Frontiers in immunology · 2017Review
- Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies.Frontiers in immunology · 2017Article
- B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
- Combined IL-15 and IL-12 drives the generation of CD34Oncoimmunology · 2015Article
- Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens.Nature reviews. Drug discovery · 2015Review
- Natural Killer Cell-Based Therapies Targeting Cancer: Possible Strategies to Gain and Sustain Anti-Tumor Activity.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The possibility to modulate ex vivo human NK cell differentiation towards specific phenotypes will contribute to a better understanding of NK cell differentiation and facilitate tailored production of NK cells for immunotherapy. In this study, we show that addition of a specific low dose of IL-12 to an ex vivo NK cell differentiation system from cord blood CD34(+) stem cells will result in significantly increased proportions of cells with expression of CD62L as well as KIRs and CD16 which are preferentially expressed on mature CD56(dim) peripheral blood NK cells. In addition, the cells displayed decreased expression of receptors such as CCR6 and CXCR3, which are typically expressed to a lower extent by CD56(dim) than CD56(bright) peripheral blood NK cells. The increased number of CD62L and KIR positive cells prevailed in a population of CD33(+)NKG2A(+) NK cells, supporting that maturation occurs via this subtype. Among a series of transcription factors tested we found Gata3 and TOX to be significantly downregulated, whereas ID3 was upregulated in the IL-12-modulated ex vivo NK cells, implicating these factors in the observed changes. Importantly, the cells differentiated in the presence of IL-12 showed enhanced cytokine production and cytolytic activity against MHC class I negative and positive targets. Moreover, in line with the enhanced CD16 expression, these cells exhibited improved antibody-dependent cellular cytotoxicity for B-cell leukemia target cells in the presence of the clinically applied antibody rituximab. Altogether, these data provide evidence that IL-12 directs human ex vivo NK cell differentiation towards more mature NK cells with improved properties for potential cancer therapies.
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