ArticleCancer immunology, immunotherapy : CII2015
Inhibition of induced nitric oxide synthase enhances the anti-tumor effects on cancer immunotherapy using TLR7 agonist in mice.
Article in Cancer immunology, immunotherapy : CII, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The microbiome-nitric oxide axis in cancer immunotherapy: a targeted qualitative systematic review of mechanistic and translational evidence.Frontiers in immunology · 2026Pooled it
- NO: a key player in microbiome dynamics and cancer pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- Radiotherapy Combined with Intralesional Immunostimulatory Agents for Soft Tissue Sarcomas.Seminars in radiation oncology · 2024Review
- The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023Review
- Nitric oxide, thyroglobulin, and calcitonin: unraveling the nature of thyroid nodules.Frontiers in endocrinology · 2023Article
- Innate and Adaptive Responses of Intratumoral Immunotherapy with Endosomal Toll-Like Receptor Agonists.Biomedicines · 2022Review
- Titanium Surface Characteristics Induce the Specific Reprogramming of Toll-like Receptor Signaling in Macrophages.International journal of molecular sciences · 2022Article
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.BioImpacts : BI · 2022Review
- Review
- Nitric Oxide: The Forgotten Child of Tumor Metabolism.Trends in cancer · 2017Review
- Targeting iNOS to increase efficacy of immunotherapies.Human vaccines & immunotherapeutics · 2017Article
- Anti-tumor Activity of Toll-Like Receptor 7 Agonists.Frontiers in pharmacology · 2017Review
- In Vitro Effects of Propranolol on T Helper Type 1 Cytokine Profile in Human Leukemic T Cells.International journal of hematology-oncology and stem cell research · 2016Article
- Inhibition of iNOS activity enhances the anti-tumor effects of alpha-galactosylceramide in established murine cancer model.Oncotarget · 2015Article
- The dual role of iNOS in cancer.Redox biology · 2015Review
- The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription.BMC cancer · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor (TLR) agonists have been shown to have anti-tumor activity in basic research and clinical studies. However, TLR agonist monotherapy in cancer treatment dose not sufficiently eliminate tumors. Activation of the innate immune response by TLR agonists and other pathogen-associated molecular patterns is effective for driving adaptive immunity via interleukin (IL)-12 or IL-1, but is counteracted by the simultaneous induction of immunosuppressive cytokines and other molecules, including IL-10, tumor growth factor-β, and induced nitric oxide synthase (iNOS). In the present study, we evaluated the anticancer effect of the TLR7 agonist, imiquimod (IMQ), in the absence of iNOS. The administration of IMQ in iNOS-knockout (KO) mice implanted with tumor cells significantly suppressed tumor progression as compared to that in wild-type mice and improved the survival rate. Moreover, injection with IMQ enhanced the tumor antigen-specific Th1 response in iNOS-KO mice with tumors. The enhancement of the antigen-specific Th1 response was associated with an increase in IL-2 and IL-12b expressions in the tumor-draining lymph nodes. Combination therapy with IMQ and an iNOS inhibitor also significantly inhibited tumor growth in the established tumor model. Finally, our results indicated that the enhancement of iNOS expression through the administration with TLR agonists impairs host anti-tumor immunity, while the inhibition of iNOS could enhance the therapeutic efficacy of TLR agonists via the increase in Th1 immune response.
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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.