ArticleThe Journal of clinical investigation2012
Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 1 of them a synthesis that pooled it.
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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
157 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.
- Application potential of toll-like receptors in cancer immunotherapy: Systematic review.Medicine · 2016Pooled it
- Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy.The Journal of clinical investigation · 2017Trial
- Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- The genesis of cutaneous neurogenic inflammation is a multi-step process requiring dendritic cell aggregation.Immunity · 2026Article
- The plasmacytoid dendritic cell paradox in cancer: impaired type I interferon responses in a nucleic acid-rich tumor microenvironment.Frontiers in immunology · 2026Review
- Deciphering the Role of Mast Cells in HPV-Related Cancers.International journal of molecular sciences · 2025Review
- CIMT 2025: Report on the 22Human vaccines & immunotherapeutics · 2025Article
- Role of the TLR signaling pathway in the pathogenesis of glioblastoma multiforme with an emphasis on immunotherapy.Biochemistry and biophysics reports · 2025Review
- TLR7/8 ligands R848 and imiquimod induce differentiation of bone marrow cells from patients with myelodysplastic syndrome towards mature neutrophils.Scientific reports · 2025Article
- Multi-omics and functional characterization of the tumor-killing capacity of Imiquimod-activated plasmacytoid dendritic cells.iScience · 2025Article
- Performance of Imidazoquinoline Glycoconjugate BAIT628 as a TLR7 Agonist Prodrug for Prostate Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Enhancing anti-tumor immunity through intratumoral combination therapy with amphiphilic conjugates of oxaliplatin and imidazoquinoline TLR7/8 agonist.RSC advances · 2025Article
- Systemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor suppression by c-Jun-dependent IL-12 expression in dendritic cells.Nature cancer · 2025Article
- Systemic IFN-I Synergizes with Topical TLR7/8 Agonists to Suppress Metastatic Tumors.Research (Washington, D.C.) · 2025Article
- Mast Cells in the Solid Tumor Microenvironment: Multiple Roles and Targeted Therapeutic Potential.Oncology research · 2025Review
- Mast cell - tumor cell interaction related gene and microRNA expression profiles in oral squamous cell carcinoma.Frontiers in oncology · 2025Article
- The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond.Cellular & molecular immunology · 2024Review
- Immune mediated support of metastasis: Implication for bone invasion.Cancer communications (London, England) · 2024Review
- Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases.Cancer research communications · 2024Article
- TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation.BMC immunology · 2024Article
97 more citing papers are in PubMed but not listed here.
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8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imiquimod is a synthetic compound with antitumor properties; a 5% cream formulation is successfully used to treat skin tumors. The antitumor effect of imiquimod is multifactorial, although its ability to modulate immune responses by triggering TLR7/8 is thought to be key. Among the immune cells suggested to be involved are plasmacytoid DCs (pDCs). However, a direct contribution of pDCs to tumor killing in vivo and the mechanism of their recruitment to imiquimod-treated sites have never been demonstrated. Using a mouse model of melanoma, we have now demonstrated that pDCs can directly clear tumors without the need for the adaptive immune system. Topical imiquimod treatment led to TLR7-dependent and IFN-α/β receptor 1-dependent (IFNAR1-dependent) upregulation of expression of the chemokine CCL2 in mast cells. This was essential to induce skin inflammation and for the recruitment of pDCs to the skin. The recruited pDCs were CD8α+ and induced tumor regression in a TLR7/MyD88- and IFNAR1-dependent manner. Lack of TLR7 and IFNAR1 or depletion of pDCs or CD8α+ cells from tumor-bearing mice completely abolished the effect of imiquimod. TLR7 was essential for imiquimod-stimulated pDCs to produce IFN-α/β, which led to TRAIL and granzyme B secretion by pDCs via IFNAR1 signaling. Blocking these cytolytic molecules impaired pDC-mediated tumor killing. Our results demonstrate that imiquimod treatment leads to CCL2-dependent recruitment of pDCs and their transformation into a subset of killer DCs able to directly eliminate tumor cells.
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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.