ArticleJournal of cancer research and clinical oncology2017
Dual activation of Toll-like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer.
Article in Journal of cancer research and clinical oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Calcium Electrochemotherapy and Challenges in Combined Treatment with Dendritic Cell Vaccination.Pharmaceutics · 2025Article
- Toll-like receptors in breast cancer immunity and immunotherapy.Frontiers in immunology · 2024Review
- Targeting FOXP3 Tumor-Intrinsic Effects Using Adenoviral Vectors in Experimental Breast Cancer.Viruses · 2023Article
- Therapeutic Cancer Vaccines-Antigen Discovery and Adjuvant Delivery Platforms.Pharmaceutics · 2022Review
- The Role of Toll-like Receptor Agonists and Their Nanomedicines for Tumor Immunotherapy.Pharmaceutics · 2022Review
- MuSyC dosing of adjuvanted cancer vaccines optimizes antitumor responses.Frontiers in immunology · 2022Article
- Immune control by amino acid catabolism during tumorigenesis and therapy.Nature reviews. Cancer · 2019Review
- PD-1 blockade enhances radio-immunotherapy efficacy in murine tumor models.Journal of cancer research and clinical oncology · 2018Article
- Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeSince combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models.
methodsDCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas.
resultsCpG-DCs improved the survival of tumor-bearing mice, reduced the development of lung metastases and generated immunological memory. However, dual activation of TLRs impaired the efficacy of DC vaccines. In vitro, we found that R848 inhibited CpG-mediated maturation of murine DCs. A positive feedback loop in TLR9 mRNA expression was observed upon CpG stimulation that was inhibited in the presence of R848. Impaired activation of NF-κB was detected when TLR9 and TLR7 were simultaneously activated. Blockade of nitric oxide synthase (NOS) and indoleamine-pyrrole-2,3-dioxygenase (IDO) improved the activation of CpG-DCs. When we evaluated the effect of combined activation of TLR9 and TLR7 in human DCs, we found that R848 induced robust DC activation that was inhibited by TLR9 agonists.
conclusionsThese observations provide insight in the biology of TLR9 and TLR7 crosstalk and suggest caution in the selection of agonists for multiple TLR stimulation. Blockade of NOS and IDO could improve the maturation of antitumor DC vaccines. R848 could prove a useful adjuvant for DC vaccines in human patients.
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