ArticleJournal for immunotherapy of cancer2020
Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
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Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- TIGIT Expression and Its Implications in Non-Small-Cell Lung Cancer Progression and Therapy: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Pooled it
- The Right Key, the Wrong Lock: TIGIT Checkpoint Blockade and the Road to Precision Immunotherapy.Pharmaceutics · 2026Review
- Molecular Imaging in Pancreatic Cancer: Current Applications and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Nectin-4 expression in clear cell renal cell carcinoma.Scientific reports · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Yeast surface display-based screening and preliminary characterization of nectin-4-targeting nanobodies for bladder cancer.BMC biotechnology · 2026Article
- Emerging Immunotherapy and Antibody-Derived Therapeutics for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Review.Cancers · 2026Review
- Elevated T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT) Expression and Immune Cell Dysfunction Characterize Complex Proteins Associated With SET1 (COMPASS)-Like Complex Gene-Mutated Pancreatic Ductal Adenocarcinoma (PDAC).Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- The hypoxic ECM and neutrophils in MIBC immunotherapy resistance.Nature reviews. Urology · 2026Review
- Treatment strategies for locally advanced and metastatic urothelial carcinoma based on molecular profiles: A Review.Histology and histopathology · 2026Review
- A Case of Upper Tract Urothelial Carcinoma With Neuroendocrine Differentiation Successfully Treated With Enfortumab Vedotin and Pembrolizumab.IJU case reports · 2026Article
- Comparative safety analysis of enfortumab vedotin and pembrolizumab: monotherapy vs. combination therapy insights from FDA adverse event reporting system data.World journal of urology · 2026Article
- Nectin-4 reduces T cell effector function and is a therapeutic target in pancreatic cancer.JCI insight · 2026Article
- Association of TIGIT and CD155 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, MSI Status, and Cytokine Profiles in Colorectal Cancer.International journal of molecular sciences · 2026Article
- Targeting T cell exhaustion in colorectal cancer: emerging roles of LAG-3, TIM-3, and TIGIT signaling in overcoming immunotherapy resistance.Cell communication and signaling : CCS · 2026Review
- Site-specific differences in Nectin-4 expression and associated immune contexture in advanced urothelial carcinoma: implications for Nectin-4-targeted ADCs.Therapeutic advances in medical oncology · 2026Article
- Topographical and stage-related expression of nectin-4 in prostate cancer.Central European journal of urology · 2026Article
- Leveraging the heterogeneity of the NK cell repertoire for the development of immunotherapies for acute leukemia.Journal of translational medicine · 2025Review
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.
methodsWe stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo.
resultsWe identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo.
conclusionWe discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy.
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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.