ArticleImmunology2009
Tumour-derived prostaglandin E and transforming growth factor-beta synergize to inhibit plasmacytoid dendritic cell-derived interferon-alpha.
Article in Immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- TGF-β in hematologic malignancies: molecular functions and clinical applications.Frontiers in immunology · 2026Review
- Mechanisms of Immune Evasion, Dissemination, and Persistence in Leishmania amazonensis Infection.Parasite immunology · 2026Review
- The plasmacytoid dendritic cell paradox in cancer: impaired type I interferon responses in a nucleic acid-rich tumor microenvironment.Frontiers in immunology · 2026Review
- Dendritic cells: the central partner for cancer immunity.Oncoimmunology · 2025Review
- Review
- New insights into the role of IFN-α/β and TLR7/8/9 in cancer immunotherapy and systemic autoimmunity.Journal for immunotherapy of cancer · 2025Review
- Adipose-derived mesenchymal stromal/stem cells in type 1 diabetes treatment.Communications biology · 2025Review
- Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Type III interferon primes pDCs for TLR7 activation and antagonizes immune suppression mediated by TGF-β and PGE2.Nature communications · 2025Article
- Overview of dendritic cells subsets and their involvement in immune-related pathological disease.BioImpacts : BI · 2025Review
- Plasmacytoid dendritic cells at the forefront of anti-cancer immunity: rewiring strategies for tumor microenvironment remodeling.Journal of experimental & clinical cancer research : CR · 2024Review
- The Multifaceted Functionality of Plasmacytoid Dendritic Cells in Gastrointestinal Cancers: A Potential Therapeutic Target?Cancers · 2024Review
- Inhibitory receptors of plasmacytoid dendritic cells as possible targets for checkpoint blockade in cancer.Frontiers in immunology · 2024Review
- Evaluation of tumor response to immune checkpoint inhibitors by a 3D immunotumoroid model.Frontiers in immunology · 2024Article
- The Role of Exosome-Derived microRNA on Lung Cancer Metastasis Progression.Biomolecules · 2023Review
- Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity.Cancer biology & medicine · 2023Review
- Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1/PD-L1 immunotherapy for solid cancers.Molecular cancer · 2023Review
- Impaired activation of plasmacytoid dendritic cellsFrontiers in immunology · 2023Article
- Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In previous studies we reported that plasmacytoid dendritic cells (PDC) infiltrating head and neck cancer tissue are functionally impaired, but the molecular basis for the functional deficiency remained unclear. Here we demonstrate that tumour-derived prostaglandin E2 (PGE(2)) and transforming growth factor-beta (TGF-beta) increase interleukin-8 (IL-8) but synergistically inhibit interferon-alpha (IFN-alpha) and tumour necrosis factor (TNF) production of Toll-like receptor 7 (TLR7)- and Toll-like receptor 9 (TLR9)-stimulated PDC. The inhibitory effect of PGE(2) could be mimicked by the induction of cyclic AMP (cAMP) and by inhibitors of cyclooxygenase. The contribution of tumour-derived TGF-beta was confirmed by the TGF-beta antagonist SB-431542. Suppression of tumour-derived PGE(2) and TGF-beta restored TLR-induced IFN-alpha production of PDC. Additionally, PGE(2)- and TGF-beta-treated PDC display a 'tolerogenic' phenotype because of a downregulation of CD40 accompanied by an upregulation of CD86. Finally, in TLR-stimulated PDC, PGE(2) and TGF-beta reduce the CCR7:CXCR4 ratio, suggesting that PDC are impaired in their ability to migrate to tumour-draining lymph nodes but are retained in stromal cell-derived factor 1 (SDF-1)-expressing tissues. Based on these data, cyclooxygenase inhibitors and TGF-beta antagonists may improve TLR7- and TLR9-based tumour 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.