ArticleProceedings of the National Academy of Sciences of the United States of America2016
Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- SingleInternational journal of oncology · 2026Article
- Nanoparticulate Immunoactive Complex for Local Chemoimmunotherapy: From Murine Models to Pilot Canine Study.Cancer research communications · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Flagellins as Vaccine Adjuvants and Cancer Immunotherapy: Recent Advances and Future Prospects.Immunology · 2025Review
- The role of NK cells in regulating tumorimmunity: current state, challenges and future strategies.Cancer cell international · 2025Review
- Flagellin engineering enhances CAR-T cell function by reshaping tumor microenvironment in solid tumors.Journal for immunotherapy of cancer · 2025Article
- Synthetic vectors for activating the driving axis of ferroptosis.Nature communications · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8Cancer immunology, immunotherapy : CII · 2024Article
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- Microbial sensing in the intestine.Protein & cell · 2023Review
- The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer.Cancer biology & medicine · 2023Article
- TLR5 agonists enhance anti-tumor immunity and overcome resistance to immune checkpoint therapy.Communications biology · 2023Article
- Repurposing of Commercially Existing Molecular Target Therapies to Boost the Clinical Efficacy of Immune Checkpoint Blockade.Cancers · 2022Review
- Inhibiting the biogenesis of myeloid-derived suppressor cells enhances immunotherapy efficacy against mammary tumor progression.The Journal of clinical investigation · 2022Article
- Stem Cells as Target for Prostate cancer Therapy: Opportunities and Challenges.Stem cell reviews and reports · 2022Review
- Review
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5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of an anticancer innate immune response is highly desirable because of its inherent ability to generate an adaptive antitumor T-cell response. However, insufficient safety of innate immune modulators limits clinical use to topical applications. Toll-like receptor 5 (TLR5) agonists are favorably positioned as potential systemic immunotherapeutic agents because of unusual tissue specificity of expression, uniquely safe profile of induced cytokines, and antitumor efficacy demonstrated in a number of animal models. Here, we decipher the molecular and cellular events underlying the metastasis suppressive activity of entolimod, a clinical stage TLR5 agonist that activates NF-κB-, AP-1-, and STAT3-driven immunomodulatory signaling pathways specifically within the liver. Used as a single agent in murine colon and mammary metastatic cancer models, entolimod rapidly induces CXCL9 and -10 that support homing of blood-borne CXCR3-expressing NK cells to the liver predominantly through an IFN-γ signaling independent mechanism. NK cell-dependent activation of dendritic cells is followed by stimulation of a CD8(+) T-cell response, which exert both antimetastatic effect of entolimod and establishment of tumor-specific and durable immune memory. These results define systemically administered TLR5 agonists as organ-specific immunoadjuvants, enabling efficient antitumor vaccination that does not depend on identification of tumor-specific antigens.
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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.