ArticleThe EMBO journal2023
The CTLA-4 immune checkpoint protein regulates PD-L1:PD-1 interaction via transendocytosis of its ligand CD80.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- CD80 as an Important Immune Mediator and Therapeutic Target in Atherosclerosis.International journal of molecular sciences · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Potentiation of the altered immune microenvironment following RF ablation of murine distant tumors with CTLA-4 immunotherapy.European radiology experimental · 2026Article
- Splenic treg-related immunoregulation in the spleen-brain axis of alzheimer's disease: mechanisms and translational strategies.Molecular biology reports · 2026Review
- Inhibition of LARP4-mediated quiescence exit of naive CD4Nature biomedical engineering · 2026Article
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Molecular Mechanisms of Resistance to Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.Cells · 2026Review
- Immune-modified exosome vaccine loaded with liver cancer epitope peptides induces potent and specific antitumor immunity.Journal of nanobiotechnology · 2026Article
- Expression of Immune CheckpointsTurkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- Colorectal cancer-derived extracellular vesicles: at the crossroads of the tumor microenvironment and gut microbiota.Frontiers in immunology · 2026Review
- Immune checkpoint crosstalk: CTLA-4/CD80 engagement as a predictor of anti-PD-1/PD-L1 therapy outcome in NSCLC.Frontiers in immunology · 2026Article
- CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.Current gene therapy · 2026Review
- VSIG2 as a novel immunosuppressive ligand interacts with Nectin-2 to regulate T cell responses.Journal of neuroinflammation · 2025Article
- XPR1 promotes ovarian cancer growth and regulates MHC-I through autophagy.Genes & diseases · 2025Article
- Clinical Impact of CTLA-4 Single-Nucleotide Polymorphism in DLBCL Patients Treated with CAR-T Cell Therapy.Current oncology (Toronto, Ont.) · 2025Article
- Overview of immune checkpoint inhibitor associated myocarditis mechanisms diagnostics and treatment.Frontiers in immunology · 2025Review
- Rigid, bivalent CTLA-4 binding to CD80 is required to disrupt the cis CD80/PD-L1 interaction.Cell reports · 2024Article
- Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine.Nature reviews. Clinical oncology · 2024Review
- Intercellular Transfer of Immune Regulatory Molecules Via Trogocytosis.Results and problems in cell differentiation · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 4 countries.
Funding
Abstract
CTLA-4 and PD-1 are key immune checkpoint receptors that are targeted in the treatment of cancer. A recently identified physical interaction between the respective ligands, CD80 and PD-L1, has been shown to block PD-L1/PD-1 binding and to prevent PD-L1 inhibitory functions. Since CTLA-4 is known to capture and degrade its ligands via transendocytosis, we investigated the interplay between CD80 transendocytosis and CD80/PD-L1 interaction. We find that transendocytosis of CD80 results in a time-dependent recovery of PD-L1 availability that correlates with CD80 removal. Moreover, CD80 transendocytosis is highly specific in that only CD80 is internalised, while its heterodimeric PD-L1 partner remains on the plasma membrane of the antigen-presenting cell (APC). CTLA-4 interactions with CD80 do not appear to be inhibited by PD-L1, but efficient removal of CD80 requires an intact CTLA-4 cytoplasmic domain, distinguishing this process from more general trogocytosis and simple CTLA-4 binding to CD80/PD-L1 complexes. These data are consistent with CTLA-4 acting as modulator of PD-L1:PD-1 interactions via control of CD80.
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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.