ArticleProceedings of the National Academy of Sciences of the United States of America2017
Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 104 citations in OpenAlex.
- Regulatory T cells in the skin: Origin, function, and plasticity.JID innovations : skin science from molecules to population health · 2026Review
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- A fully human afucosylated anti-GARP antibody PBA-0111 drives anti-tumor immunity through combined ADCC induction and TGF-β1 pathway blockade.Frontiers in immunology · 2026Article
- Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression.Frontiers in cell and developmental biology · 2026Article
- Article
- GARP-expressing Tregs as a source of immunosuppressive TGF-β1 in human tumors.Cancer immunology, immunotherapy : CII · 2025Article
- Biomechanics of the tumor extracellular matrix and regulatory T cells: regulatory mechanisms and potential therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Distinct immune cell infiltration patterns in pancreatic ductal adenocarcinoma (PDAC) exhibit divergent immune cell selection and immunosuppressive mechanisms.Nature communications · 2025Article
- Harnessing the biology of regulatory T cells to treat disease.Nature reviews. Drug discovery · 2025Review
- Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization.Journal of experimental & clinical cancer research : CR · 2025Article
- Parkinson Disease -Targeted Nanocapsules for Synergistic Treatment: Combining Dopamine Replacement and Neuroinflammation Mitigation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Advancing immunotherapy for melanoma: the critical role of single-cell analysis in identifying predictive biomarkers.Frontiers in immunology · 2024Review
- Further knowledge and developments in resistance mechanisms to immune checkpoint inhibitors.Frontiers in immunology · 2024Review
- Comparison of Transcriptomic Analysis of the Conjunctiva in Glaucoma-Treated Eyes with Dry Eyes and Healthy Controls.Biomolecules · 2023Article
- De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.Nature communications · 2023Article
- Radiomics for characterization of the glioma immune microenvironment.NPJ precision oncology · 2023Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-β1 production. RGD-binding integrins were shown to activate TGF-β1 in several non-T cell types. Here we show that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. We also show that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. Finally, a blocking antibody against β8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-β1 activation on the surface of human Tregs implies an interaction between the integrin αVβ8 and GARP/latent TGF-β1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin β8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.
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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.