ArticleNature communications2023
TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- CD4Sensors (Basel, Switzerland) · 2026Pooled it
- TIGIT Expression and Its Implications in Non-Small-Cell Lung Cancer Progression and Therapy: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Therapeutic bacteria-trained NK cells confer long-term protection against cancer metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Beyond PD-1/PD-L1: Reprogramming the Gynecologic Tumor Microenvironment by Targeting TIGIT and Myeloid Suppression.International journal of molecular sciences · 2026Review
- Advancements in Immune Checkpoint-Based Immunotherapy for Triple-Negative Breast Cancer.Current issues in molecular biology · 2026Review
- B-cell lymphocytosis and reprogramming due to biallelic CARD11 mutations.The Journal of allergy and clinical immunology · 2026Article
- Antibody screening for tumor and immune hotspot targets: The frontier of new methods and technologies.Journal of pharmaceutical analysis · 2026Review
- Computational screening for natural compounds as potential immune checkpoint inhibitors against TIGIT, a new avenue in cancer immunotherapy.Molecular diversity · 2026Article
- T Cell Exhaustion in Hepatocellular Carcinoma: A Substantial Barrier in Immunotherapy.Journal of cellular and molecular medicine · 2026Review
- TIGIT disruption rescues the antitumor activity of low avidity TCR-engineered T cells by increasing TCR signal strength.Nature communications · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- An evolutionary T119R substitution in the macaque T-cell immunoreceptor TIGIT enables proteolytic shedding and reveals clinical antibody vulnerabilities.The Journal of biological chemistry · 2026Article
- Next-generation immunotherapies for head and neck squamous cell carcinoma: targeting novel immune checkpoints.Annals of medicine · 2025Review
- Integrated bulk and single-cell transcriptomic profiling reveals NECTIN-TIGIT interaction underlies T cell exhaustion in papillary thyroid carcinoma.Clinical and experimental medicine · 2025Article
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 2025Article
- TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.Cancer immunology research · 2025Article
- LAG3+ CD8+ T cell subset drives HR+/HER2- breast cancer reduction in bispecific antibody armed activated T cell therapy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- TIGIT antibody with PVR competitive ability enhances cancer immunotherapy and capable of eliciting anti-tumour immune memory.British journal of cancer · 2025Article
- Nano-org, a functional resource for single-molecule localisation microscopy data.Nature communications · 2025Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT's intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action.
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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.