ArticleJournal of immunology (Baltimore, Md. : 1950)2010
NKG2D initiates caspase-mediated CD3zeta degradation and lymphocyte receptor impairments associated with human cancer and autoimmune disease.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- The Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes.Biomedicines · 2024Article
- Immune evasion by proteolytic shedding of natural killer group 2, member D ligands inFrontiers in immunology · 2024Article
- SUMOylation and related post-translational modifications in natural killer cell anti-cancer responses.Frontiers in cell and developmental biology · 2023Review
- Antibody targeting tumor-derived soluble NKG2D ligand sMIC reprograms NK cell homeostatic survival and function and enhances melanoma response to PDL1 blockade therapy.Journal of hematology & oncology · 2020Article
- Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D.Frontiers in immunology · 2020Article
- Defects at the Posttranscriptional Level Account for the Low TCRJournal of immunology research · 2020Article
- Research Progress on NK Cell Receptors and Their Signaling Pathways.Mediators of inflammation · 2020Review
- Antibody targeting tumor-derived soluble NKG2D ligand sMIC provides dual co-stimulation of CD8 T cells and enables sMICJournal for immunotherapy of cancer · 2019Article
- Downregulation of CD3ζ in NK Cells from Systemic Lupus Erythematosus Patients Confers a Proinflammatory Phenotype.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- NKG2D and its ligands in cancer.Current opinion in immunology · 2018Review
- NKG2D Ligands-Critical Targets for Cancer Immune Escape and Therapy.Frontiers in immunology · 2018Review
- NKG2D: A Master Regulator of Immune Cell Responsiveness.Frontiers in immunology · 2018Review
- Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.International journal of molecular sciences · 2017Review
- Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells.Neoplasia (New York, N.Y.) · 2017Article
- Antibody-mediated neutralization of soluble MIC significantly enhances CTLA4 blockade therapy.Science advances · 2017Article
- MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue.British journal of cancer · 2017Article
- Chronic NKG2D EngagementFrontiers in immunology · 2017Article
- Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2016Article
- Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients.Oncoimmunology · 2016Article
- Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer.Immunology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Deficiencies of the T cell and NK cell CD3ζ signaling adapter protein in patients with cancer and autoimmune diseases are well documented, but mechanistic explanations are fragmentary. The stimulatory NKG2D receptor on T and NK cells mediates tumor immunity but can also promote local and systemic immune suppression in conditions of persistent NKG2D ligand induction that include cancer and certain autoimmune diseases. In this paper, we provide evidence that establishes a causative link between CD3ζ impairment and chronic NKG2D stimulation due to pathological ligand expression. We describe a mechanism whereby NKG2D signaling in human T and NK cells initiates Fas ligand/Fas-mediated caspase-3/-7 activation and resultant CD3ζ degradation. As a consequence, the functional capacities of the TCR, the low-affinity Fc receptor for IgG, and the NKp30 and NKp46 natural cytotoxicity receptors, which all signal through CD3ζ, are impaired. These findings are extended to ex vivo phenotypes of T and NK cells among tumor-infiltrating lymphocytes and in peripheral blood from patients with juvenile-onset lupus. Collectively, these results indicate that pathological NKG2D ligand expression leads to simultaneous impairment of multiple CD3ζ-dependent receptor functions, thus offering an explanation that may be applicable to CD3ζ deficiencies associated with diverse disease conditions.
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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.