ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Membrane-type 6 matrix metalloproteinase regulates the activation-induced downmodulation of CD16 in human primary NK cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 83 citations in OpenAlex.
- Natural killer (NK) cells with downregulated activating receptors and IL-10 production promote Trypanosoma cruzi T-cell responses in subjects in the Chronic phase of Trypanosoma cruzi infection: An exploratory immunological analysis.PLoS neglected tropical diseases · 2026Article
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Phenotypic, proteomic, and functional analyses of cytokine-induced memory-like NK cells show two distinct subsets based on CD16 expression.Scientific reports · 2025Article
- CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells.European journal of immunology · 2025Article
- Article
- Modulation of the malignant behavior of tongue squamous cell carcinoma cells by matrix metallopeptidase 25 through the NF-κB pathway.Histology and histopathology · 2025Article
- Cell-targeted PD-1 agonists are potent NK-cell inhibitors.Frontiers in immunology · 2025Article
- Emerging Innate Immune Cells in Cancer Immunotherapy: Promises and Challenges.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- TLR9 agonism differentially impacts human NK cell-mediated direct killing and antibody-dependent cell-mediated cytotoxicity.Scientific reports · 2024Article
- A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Human NK cells and cancer.Oncoimmunology · 2024Review
- Review
- Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function.Cancer immunology research · 2023Article
- MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity.JCI insight · 2023Article
- Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics.Science advances · 2023Article
- Impact of SARS-CoV-2 vaccination on FcγRIIIA/CD16 dynamics in Natural Killer cells: relevance for antibody-dependent functions.Frontiers in immunology · 2023Article
- The multifaceted roles of matrix metalloproteinases in lung cancer.Frontiers in oncology · 2023Review
- P2X7 receptor activation impairs antitumour activity of natural killer cells.British journal of pharmacology · 2023Article
- Natural Killer Cell Engagers (NKCEs): a new frontier in cancer immunotherapy.Frontiers in immunology · 2023Review
- The prospect of genetically engineering natural killer cells for cancer immunotherapy.Biology open · 2022Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
CD16 (FcγRIIIa), the low-affinity receptor for IgG, expressed by the majority of human NK cells, is a potent activating receptor that facilitates Ab-dependent cell-mediated cytotoxicity (ADCC). ADCC dysfunction has been linked to cancer progression and poor prognosis for chronic infections, such as HIV; thus, understanding how CD16 expression is regulated by NK cells has clinical relevance. Importantly, CD16 cell-surface expression is downmodulated following NK cell activation and, in particular, exposure to stimulatory cytokines (IL-2 or IL-15), likely owing to the action of matrix metalloproteinases (MMPs). In this article, we identify membrane-type 6 (MT6) MMP (also known as MMP25) as a proteinase responsible for CD16 downmodulation. IL-2-induced upregulation of MT6/MMP25 cell-surface expression correlates with CD16 downmodulation. MT6/MMP25, sequestered in intracellular compartments in unstimulated NK cells, translocates to the cell surface after stimulation; moreover, it polarizes to the effector-target cell interface of the CD16-mediated immunological synapse. siRNA-mediated disruption of MT6/MMP25 expression enhances the ADCC capacity of NK cells, emphasizing the important functional role of MT6/MMP25 in the regulation of ADCC activity. Thus, this study uncovers a previously unknown role of MT6/MMP25 in human NK cells, and suggests that inhibition of MT6/MMP25 activity could improve ADCC efficacy of therapeutically administered NK cells that require IL-2 for culture and expansion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.