ArticleNature immunology2018
LAG-3 inhibits the activation of CD4
Article in Nature immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 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
179 citing papers in PubMed.
- Clinical response and pathway-specific correlates following TIGIT-LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial.Nature cancer · 2024Trial
- CD4Clinical and experimental immunology · 2021Trial
- LAG3 checkpoint function and its mechanism of action in therapeutic targeting.Nature reviews. Immunology · 2026Review
- Immune checkpoint crosstalk between LAG-3 and CD39/CD73 in glioblastoma: dual-pathway regulation of metabolic exhaustion and therapeutic reversal strategies.Journal of the Egyptian National Cancer Institute · 2026Review
- Distinct cytokines regulate gene expression and anti-tumor activity in regenerated CD8iScience · 2026Article
- A Potent Single-Domain Antibody Targeting LAG-3 for Efficient Tumor Immunotherapy.Current issues in molecular biology · 2026Article
- The subset of M1-paired MHC class II conformers is critical for CD4+ T cell activation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Regulatory B cells andBiomolecules & biomedicine · 2026Article
- Harnessing tumor immune checkpoints for autoimmune disease therapeutics.Frontiers in immunology · 2026Review
- Sabotaging TCR signaling-LAG3 interferes with the CD3ε-LCK interaction.Cell research · 2026Article
- Review
- Immune biomarkers for head and neck cancer.Cancer immunology, immunotherapy : CII · 2025Review
- Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model.Oncoimmunology · 2025Article
- Spatial Proximity of LAG-3 and T Cell Receptor: A New Paradigm for T Cell Suppression.MedComm · 2025Article
- Novel Therapeutics for Hepatocellular Carcinoma.Clinics in liver disease · 2025Review
- Regulatory Role of FGL-1 in Interorgan Communication by Controlling T Cell Homeostasis During the Onset of Sjögren Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Trends in immunotherapy for oral squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Genetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks.Nature genetics · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Multi-engineered T cell vaccine boosting TCR-T cell therapy enhances anti-tumor function and eradicates heterogeneous solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
119 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of tumor immunotherapy targeting the inhibitory co-receptors PD-1 and CTLA-4 has indicated that many other co-receptors might be potential druggable targets, despite limited information about their functional differences. Here we identified a unique target selectivity for the inhibitory co-receptor LAG-3 that was intrinsic to its immunoregulatory roles. Although LAG-3 has been reported to recognize major histocompatibility complex (MHC) class II, it did not recognize MHC class II universally; instead, we found that it selectively recognized stable complexes of peptide and MHC class II (pMHCII). LAG-3 did not directly interfere with interactions between the co-receptor CD4 and MHC class II or between the T cell antigen receptor and MHC class II. Instead, LAG-3 preferentially suppressed T cells responsive to stable pMHCII by transducing inhibitory signals via its intracellular region. Thus, LAG-3 might function more selectively than previously thought and thereby maintain tolerance to dominant autoantigens.
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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.