ArticleJCI insight2018
CD226 opposes TIGIT to disrupt Tregs in melanoma.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
130 citing papers in PubMed, 197 citations in OpenAlex.
- TIGITCancers · 2026Article
- The Right Key, the Wrong Lock: TIGIT Checkpoint Blockade and the Road to Precision Immunotherapy.Pharmaceutics · 2026Review
- IFITM3 promotes an M2-like tumor-supportive microenvironment in acute myeloid leukemia.Medical oncology (Northwood, London, England) · 2026Article
- Beyond PD-1/PD-L1: Reprogramming the Gynecologic Tumor Microenvironment by Targeting TIGIT and Myeloid Suppression.International journal of molecular sciences · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Protein-level profiling of TIGIT axis components in human PDAC reveals immune-suppressive expression patterns.Cancer immunology, immunotherapy : CII · 2026Article
- Specific depletion of TIGITJournal for immunotherapy of cancer · 2026Article
- Single-cell and multi-omic characterization of ex vivo expanded ASTRLs from stable kidney transplant recipients reveals a regulatory T cell phenotype.Scientific reports · 2026Article
- Distinct remission immune architectures under rituximab and azathioprine in AQP4-IgG-positive neuromyelitis optica spectrum disorder.Frontiers in immunology · 2026Article
- [Guardians of Immune Tolerance: Regulatory T Cells].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 2025Article
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- TIGIT antibody with PVR competitive ability enhances cancer immunotherapy and capable of eliciting anti-tumour immune memory.British journal of cancer · 2025Article
- TYK2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation.Cell reports. Medicine · 2025Article
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- Advances and Challenges in Immunotherapy for Metastatic Uveal Melanoma: Clinical Strategies and Emerging Targets.Journal of clinical medicine · 2025Review
- The Immune Regulatory Functions of CD226 and Its Implications in Immune-Mediated Diseases.Biomolecules · 2025Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
CD4+ Tregs impede T cell responses to tumors. They express multiple inhibitory receptors that support their suppressive functions, including T cell Ig and ITIM domain (TIGIT). In melanoma patients, we show that Tregs exhibit increased TIGIT expression and decreased expression of its competing costimulatory receptor CD226 as compared with CD4+ effector T cells, resulting in an increased TIGIT/CD226 ratio. Tregs failed to upregulate CD226 upon T cell activation. TIGIT+ Tregs are highly suppressive, stable, and enriched in tumors. TIGIT and CD226 oppose each other to augment or disrupt, respectively, Treg suppression and stability. A high TIGIT/CD226 ratio in Tregs correlates with increased Treg frequencies in tumors and poor clinical outcome upon immune checkpoint blockade. Altogether, our findings show that a high TIGIT/CD226 ratio in Tregs regulates their suppressive function and stability in melanoma. They provide the rationale for novel immunotherapies to activate CD226 in Tregs together with TIGIT blockade to counteract Treg suppression in cancer patients.
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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.