ArticleCancer research2013
TLR9 signaling in the tumor microenvironment initiates cancer recurrence after radiotherapy.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.International journal of molecular sciences · 2021Pooled it
- Does acute inflammation triggered by infection promote cancer progression?PLoS biology · 2026Review
- TLR8 agonists remodel the tumor immune microenvironment through PF4-dependent T cell recruitment and ancillary mechanisms.Cancer immunology, immunotherapy : CII · 2026Article
- Toll-like receptors: versatile players in tumor.Frontiers in immunology · 2026Review
- Neutrophil-specific targeting of STAT3 impairs tumor progression via the expansion of cytotoxic CD8Signal transduction and targeted therapy · 2025Article
- Plasma Proteomic Analysis Reveals Complement System Changes in Irradiated Female BALB/c Mice during Mammary Carcinogenesis.Cancer research communications · 2025Article
- TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025Review
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- Local CpG-Molecular therapy. Nucleic acids · 2024Article
- Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.Expert reviews in molecular medicine · 2024Review
- How Toll-like Receptor 9 Plays a Key Role in the Development of Gastric Cancer and Is Linked to Epstein-Barr Virus Infection.Cancers · 2023Article
- Myeloid MyD88 restricts CD8Scientific reports · 2023Article
- Recent Progress of Gold-Based Nanostructures towards Future Emblem of Photo-Triggered Cancer Theranostics: A Special Focus on Combinatorial Phototherapies.Pharmaceutics · 2023Review
- The Formation of NETs and Their Mechanism of Promoting Tumor Metastasis.Journal of oncology · 2023Review
- Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives.Frontiers in immunology · 2023Review
- Aging-associated accumulation of mitochondrial DNA mutations in tumor origin.Life medicine · 2022Review
- Radiotherapy combined with immunotherapy: the dawn of cancer treatment.Signal transduction and targeted therapy · 2022Review
- Lipopolysaccharides increase the risk of colorectal cancer recurrence and metastasis due to the induction of neutrophil extracellular traps after curative resection.Journal of cancer research and clinical oncology · 2021Article
- Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer.Nature communications · 2021Article
- Targeted In Vivo Delivery of NF-κB Decoy Inhibitor Augments Sensitivity of B Cell Lymphoma to Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Cancer radiotherapy may be immunogenic, but it is unclear why its immunogenic effects are rarely sufficient to prevent tumor recurrence. Here, we report a novel Toll-like receptor 9 (TLR9)-dependent mechanism that initiates tumor regrowth after local radiotherapy. Systemic inhibition of TLR9, but not TLR4, delayed tumor recurrence in mouse models of B16 melanoma, MB49 bladder cancer, and CT26 colon cancer after localized high-dose tumor irradiation. Soluble factors in the microenvironment of regressing tumors triggered TLR9 signaling in freshly recruited myeloid cells appearing within four days of radiotherapy. The tumorigenic effects of TLR9 depended on MyD88/NF-κB-mediated upregulation of interleukin (IL)-6 expression, which in turn resulted in downstream activation of Jak/STAT3 signaling in myeloid cells. In comparing global gene expression in wild-type, TLR9-, or STAT3-deficient myeloid cells derived from irradiated tumors, we identified a unique set of TLR9/STAT3-regulated genes involved in tumor-promoting inflammation and revascularization. Blocking STAT3 function by two myeloid-specific genetic strategies corrected TLR9-mediated cancer recurrence after radiotherapy. Our results suggest that combining localized tumor irradiation with myeloid cell-specific inhibition of TLR9/STAT3 signaling may help eliminate radioresistant cancers.
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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.