ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Toll-like receptor agonist imiquimod facilitates antigen-specific CD8+ T-cell accumulation in the genital tract leading to tumor control through IFNγ.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Imiquimod enhances anti-tumor effects of CD47 targeting in oral squamous cell carcinoma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Topical vaginal drug therapy in cervical cancer management: a review of clinical trials and preclinical evidence.Medical oncology (Northwood, London, England) · 2025Review
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Review
- Tuning the fluidity and protein corona of ultrasound-responsive liposomal nanovaccines to program T cell immunity in mice.Nature communications · 2024Article
- Intratumoral IFN-γ or topical TLR7 agonist promotes infiltration of melanoma metastases by T lymphocytes expanded in the blood after cancer vaccine.Journal for immunotherapy of cancer · 2023Article
- Review
- Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.Frontiers in immunology · 2022Review
- Active immunization combined with cisplatin confers enhanced therapeutic protection and prevents relapses of HPV-induced tumors at different anatomical sites.International journal of biological sciences · 2022Article
- Key chemokines direct migration of immune cells in solid tumors.Cancer gene therapy · 2022Review
- Inflammation-Related LncRNAs Signature for Prognosis and Immune Response Evaluation in Uterine Corpus Endometrial Carcinoma.Frontiers in oncology · 2022Article
- Th17 cells inhibit CD8Journal of hematology & oncology · 2020Article
- Inducing Immunity Where It Matters: Orthotopic HPV Tumor Models and Therapeutic Vaccinations.Frontiers in immunology · 2020Review
- Blockade of PD-L1 Enhances Cancer Immunotherapy by Regulating Dendritic Cell Maturation and Macrophage Polarization.Cancers · 2019Article
- Poly(I:C) stimulation is superior than Imiquimod to induce the antitumoral functional profile of tumor-conditioned macrophages.European journal of immunology · 2019Article
- A Prime-Pull-Amplify Vaccination Strategy To Maximize Induction of Circulating and Genital-Resident Intraepithelial CD8Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Innate immunity and HPV: friends or foes.Clinics (Sao Paulo, Brazil) · 2018Article
- Genital warts treatment: Beyond imiquimod.Human vaccines & immunotherapeutics · 2018Review
- B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses.PloS one · 2018Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeImiquimod is a Toll-like receptor 7 agonist used topically to treat external genital warts and basal cell carcinoma. We examined the combination of topical imiquimod with intramuscular administration of CRT/E7, a therapeutic human papillomavirus (HPV) vaccine comprised of a naked DNA vector expressing calreticulin fused to HPV16 E7. EXPERIMENTAL
designUsing an orthotopic HPV16 E6/E7(+) syngeneic tumor, TC-1, as a model of high-grade cervical/vaginal/vulvar intraepithelial neoplasia, we assessed if combining CRT/E7 vaccination with cervicovaginal deposition of imiquimod could result in synergistic activities promoting immune-mediated tumor clearance.
resultsImiquimod induced cervicovaginal accumulation of activated E7-specific CD8(+) T cells elicited by CRT/E7 vaccination. Recruitment was not dependent upon the specificity of the activated CD8(+) T cells, but was significantly reduced in mice lacking the IFNγ receptor. Intravaginal imiquimod deposition induced upregulation of CXCL9 and CXCL10 mRNA expression in the genital tract, which are produced in response to IFNγ receptor signaling and attract cells expressing their ligand, CXCR3. The T cells attracted by imiquimod to the cervicovaginal tract expressed CXCR3 as well as CD49a, an integrin involved in homing and retention of CD8(+) T cells at mucosal sites. Our results indicate that intramuscular CRT/E7 vaccination in conjunction with intravaginal imiquimod deposition recruits antigen-specific CXCR3(+) CD8(+) T cells to the genital tract.
conclusionsSeveral therapeutic HPV vaccination clinical trials using a spectrum of DNA vaccines, including vaccination in concert with cervical imiquimod, are ongoing. Our study identifies a mechanism by which these strategies could provide therapeutic benefit. Our findings support accumulating evidence that manipulation of the tumor microenvironment can enhance the therapeutic efficacy of strategies that induce tumor-specific T cells.
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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.