ArticleClinical and experimental immunology2013
Matrix metalloproteinases inhibition promotes the polyfunctionality of human natural killer cells in therapeutic antibody-based anti-tumour immunotherapy.
Article in Clinical and experimental immunology, 2013. 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, 55 citations in OpenAlex.
- The membrane distal domain of CD16a allosterically regulates NK cell ADCC.bioRxiv : the preprint server for biology · 2026Article
- Cytokine preactivation and ADCC: a potent strategy for enhancing human NK cell effector functions against 3D tumor models.Frontiers in immunology · 2026Article
- Natural killer cell engagers: From bi-specific to tri-specific and tetra-specific engagers for enhanced cancer immunotherapy.Clinical and translational medicine · 2024Review
- Human NK cells and cancer.Oncoimmunology · 2024Review
- Killer instincts: natural killer cells as multifactorial cancer immunotherapy.Frontiers in immunology · 2023Review
- Natural killer cell immunotherapy in glioblastoma.Discover oncology · 2022Review
- Role of NK Cells in Tumor Progression.Experientia supplementum (2012) · 2022Article
- Immunomodulatory role of metalloproteases in cancers: Current progress and future trends.Frontiers in immunology · 2022Review
- A NKp80-Based Identification Strategy Reveals that CD56iScience · 2020Article
- The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass.Frontiers in immunology · 2020Article
- Role of ADAM17 as a regulatory checkpoint of CD16A in NK cells and as a potential target for cancer immunotherapy.Journal of leukocyte biology · 2019Review
- Review
- Post-translational Mechanisms Regulating NK Cell Activating Receptors and Their Ligands in Cancer: Potential Targets for Therapeutic Intervention.Frontiers in immunology · 2019Review
- Natural killers shed attachments to kill again.The Journal of cell biology · 2018Article
- Implication of Interleukin-12/15/18 and Ruxolitinib in the Phenotype, Proliferation, and Polyfunctionality of Human Cytokine-Preactivated Natural Killer Cells.Frontiers in immunology · 2018Article
- Natural killer cells in HIV-1 infection and therapy.AIDS (London, England) · 2017Review
- Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.International journal of molecular sciences · 2017Review
- Immunosenescence: limitations of natural killer cell-based cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2017Review
- Broad Impairment of Natural Killer Cells from Operationally Tolerant Kidney Transplanted Patients.Frontiers in immunology · 2017Article
- Potentiation of Natural Killer Cells for Cancer Immunotherapy: A Review of Literature.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of human natural killer (NK) cells is associated with the cleavage of CD16 from the cell surface, a process mediated by matrix metalloproteinases (MMPs). In this report, we examined whether inhibition of MMPs would lead to improved NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) function. Using an in-vitro ADCC assay, we tested the anti-tumour function of NK cells with three different therapeutic monoclonal antibodies (mAbs) in the presence of MMPs inhibitor GM6001 or its control. Loss of CD16 was observed when NK cells were co-cultured with tumour targets in the presence of specific anti-tumour antibodies, and was found particularly on the majority of degranulating NK responding cells. Treatment with MMPs inhibitors not only prevented CD16 down-regulation, but improved the quality of the responding cells significantly, as shown by an increase in the percentage of polyfunctional NK cells that are capable of both producing cytokines and degranulation. Furthermore, MMPs inhibition resulted in augmented and sustained CD16-mediated signalling, as shown by increased tyrosine phosphorylation of CD3ζ and other downstream signalling intermediates, which may account for the improved NK cell function. Collectively, our results provide a foundation for combining MMPs inhibitors and therapeutic mAbs in new clinical trials for cancer treatment.
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Registered trials
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.