ArticleThe Journal of biological chemistry2014
T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus receptor (PVR) ligand engagement suppresses interferon-γ production of natural killer cells via β-arrestin 2-mediated negative signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.
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Who cites it
156 citing papers in PubMed, 248 citations in OpenAlex.
- Overexpression of poliovirus receptor is associated with poor prognosis in head and neck squamous cell carcinoma patients.Journal of cancer research and clinical oncology · 2021Trial
- CD112 Lactylation Drives Dual Immune Evasion From CD8+ T Cells and NK Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond PD-1/PD-L1: Reprogramming the Gynecologic Tumor Microenvironment by Targeting TIGIT and Myeloid Suppression.International journal of molecular sciences · 2026Review
- CD155 and its receptors in glioma: prospects for emerging immune checkpoint inhibitors.Acta neuropathologica communications · 2026Review
- The PVR-TIGIT/CD96/CD226 axis: a novel immune checkpoint target in ovarian cancer.Frontiers in immunology · 2026Review
- Optimal transport analysis of high-dimensional flow cytometry data in immuno-oncology.Frontiers in immunology · 2026Article
- TIGITFrontiers in immunology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Immunotherapeutic strategies targeting the PVR-TIGIT/CD96/CD226 signaling pathway in glioma treatment.Annals of medicine · 2025Review
- TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.Cancer immunology research · 2025Article
- FGL1-mediated lymph node metastasis in stage T1 non-small cell lung cancer: therapeutic targeting.Experimental hematology & oncology · 2025Article
- New horizons in B-cell lymphoma immunotherapy: From immune checkpoints to precision medicine.Neoplasia (New York, N.Y.) · 2025Review
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity.JACC. Basic to translational science · 2025Article
- A Novel Class of Multi-substituted Diaryl Scaffold Derivatives Inhibit Glioblastoma Progression by Targeting CD155.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rationale of using immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in cancer treatment from a molecular perspective.Clinical and experimental medicine · 2025Review
- Attenuated immune surveillance during squamous cell transformation of pancreatic adenosquamous cancer defines new therapeutic opportunity for cancer interception.Journal for immunotherapy of cancer · 2025Article
- TIGIT deficiency promotes autoreactive CD4Nature communications · 2025Article
- Targeting Ikaros and Aiolos with pomalidomide fails to reactivate or induce apoptosis of the latent HIV reservoir.Journal of virology · 2025Article
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
96 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cell activation is well orchestrated by a wide array of NK cell receptor repertoire. T-cell immunoglobulin and ITIM domain (TIGIT) receptor was recently defined as an inhibitory receptor that is expressed on NK cells and T cells. TIGIT receptor/poliovirus receptor (PVR) ligand engagement signaling inhibits cytotoxicity mediated by NK and CD8(+) T cells. However, it is unclear how TIGIT/PVR signaling regulates cytokine secretion in NK cells. Here we show that TIGIT/PVR engagement suppresses interferon-γ (IFN-γ) production of NK cells. TIGIT transgenic NK cells generate less IFN-γ undergoing TIGIT/PVR ligation. Moreover, TIGIT knock-out NK cells produce much more IFN-γ. TIGIT/PVR ligation signaling mediates suppression of IFN-γ production via the NF-κB pathway. We identified a novel adaptor β-arrestin 2 that associates with phosphorylated TIGIT for further recruitment of SHIP1 (SH2-containing inositol phosphatase 1) through the ITT-like motif. Importantly, SHIP1, but not other phosphatases, impairs the TNF receptor-associated factor 6 (TRAF6) autoubiquitination to abolish NF-κB activation, leading to suppression of IFN-γ production in NK cells.
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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.