ArticleOncoimmunology2016
ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Targeting the NKG2D axis in head and neck squamous cell carcinoma: from molecular insights to clinical applications.Cancer cell international · 2026Review
- Evaluation of multi-antigen targeting ADCC strategies in pediatric BCP-ALL.Journal for immunotherapy of cancer · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome.International journal of molecular sciences · 2024Article
- Review
- γδ T cells in immunotherapies for B-cell malignancies.Frontiers in immunology · 2023Review
- Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.iScience · 2022Article
- Current and Emerging Approaches to Study Microenvironmental Interactions and Drug Activity in Classical Hodgkin Lymphoma.Cancers · 2022Review
- Inhibitors of ADAM10 reduce Hodgkin lymphoma cell growth in 3D microenvironments and enhance brentuximab-vedotin effect.Haematologica · 2022Article
- NKG2D Natural Killer Cell Receptor-A Short Description and Potential Clinical Applications.Cells · 2021Review
- Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021Review
- Review
- Editorial: ADAM10 in Cancer Immunology and Autoimmunity: More Than a Simple Biochemical Scissor.Frontiers in immunology · 2020Article
- Targeting ADAM10 in Cancer and Autoimmunity.Frontiers in immunology · 2020Review
- Novel Approaches and Challenges of Discovery of Exosite Modulators of a Disintegrin and Metalloprotease 10.Frontiers in molecular biosciences · 2020Review
- Target Enzymes Considered for the Treatment of Alzheimer's Disease and Parkinson's Disease.BioMed research international · 2020Review
- miR-34a as hub of T cell regulation networks.Journal for immunotherapy of cancer · 2019Article
- The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface.BMC pregnancy and childbirth · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the "A Disintegrin And Metalloproteases" (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity. Aim of the present work was to verify whether inhibition of ADAM10 in HL cells could restore the triggering of NKG2D-dependent anti-lymphoma T cell response. As no selective ADAM10 blockers have been reported so far, we synthesized the two hydroxamate compounds LT4 and MN8 with selectivity for ADAM10 over metalloproteases (MMPs), LT4 showing higher specificity for ADAM10 over ADAM17. We show that (i) HL lymph nodes (LN) and cultured HL cells express high levels of the mature active membrane form of ADAM10; (ii) ADAM10 is the major sheddase for the NKG2D-L in HL cells; (iii) the new LT4 and MN8 compounds strongly reduce the shedding of NKG2D-L by HL cell lines and enhance the binding of NKG2D receptor; (iv) of note, these new ADAM10 inhibitors increase the sensitivity of HL cell lines to NKG2D-dependent cell killing exerted by natural killer and γδ T cells. Overall, the biologic activity of LT4 and MN8 appears to be more potent than that of the commercial inhibitor GI254023X.
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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.