ArticleOncoimmunology2015
Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment.
Article in Oncoimmunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Respiratory microbiome-host interaction on lung carcinogenesis, immunity, and immunotherapy.Frontiers in immunology · 2025Review
- Article
- The Latest Approach of Immunotherapy with Endosomal TLR Agonists Improving NK Cell Function: An Overview.Biomedicines · 2022Review
- Toll-like receptor 9 agonists and combination therapies: strategies to modulate the tumour immune microenvironment for systemic anti-tumour immunity.British journal of cancer · 2022Review
- Emerging role of RNA sensors in tumor microenvironment and immunotherapy.Journal of hematology & oncology · 2022Review
- Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.Frontiers in immunology · 2022Review
- Distinct roles but cooperative effect of TLR3/9 agonists and PD-1 blockade in converting the immunotolerant microenvironment of irreversible electroporation-ablated tumors.Cellular & molecular immunology · 2021Article
- TLR3 agonists: RGC100, ARNAX, and poly-IC: a comparative review.Immunologic research · 2021Review
- Promotion of epithelial-mesenchymal transformation by hepatocellular carcinoma-educated macrophages through Wnt2b/β-catenin/c-Myc signaling and reprogramming glycolysis.Journal of experimental & clinical cancer research : CR · 2021Article
- Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression.Frontiers in cell and developmental biology · 2021Review
- Methylation Regulation ofFrontiers in oncology · 2021Article
- Aerosol 1,25-dihydroxyvitamin D3 supplementation: A strategy to boost anti-tumor innate immune activity.PloS one · 2021Article
- The Lung Microbiome: A Central Mediator of Host Inflammation and Metabolism in Lung Cancer Patients?Cancers · 2020Review
- The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy.Cellular and molecular life sciences : CMLS · 2020Review
- Pulmonary Delivery of Nanoparticle-Bound Toll-like Receptor 9 Agonist for the Treatment of Metastatic Lung Cancer.ACS nano · 2020Article
- TLR3 Expression Induces Apoptosis in Human Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2020Article
- Toll-like receptor 3 as a new marker to detect high risk early stage Non-Small-Cell Lung Cancer patients.Scientific reports · 2019Article
- Targeting Lymph Node Sinus Macrophages to Inhibit Lymph Node Metastasis.Molecular therapy. Nucleic acids · 2019Article
- Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases.Journal of immunology research · 2019Article
- Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit.British journal of cancer · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases in C57BL/6 mice. Aerosolization of CpG-ODN with Poly(I:C) into the bronchoalveolar space reduced the presence of M2-associated arginase- and IL-10-secreting macrophages in tumor-bearing lungs and increased the antitumor activity of aerosolized CpG-ODN alone against B16 lung metastases without apparent signs of toxicity or injury of the bronchial-bronchiolar structures and alveolar walls. Moreover, CpG-ODN/Poly(I:C) aerosol combined with dacarbazine, a therapeutic agent used in patients with inoperable metastatic melanoma able to exert immunostimulatory effects, led to a significant increase in antitumor activity as compared to treatments with aerosolized CpG-ODN/Poly(I:C) or dacarbazine alone. This effect was related to an enhanced recruitment and cytotoxic activity of tumor-infiltrating NK cells in the lung. Our results point to aerosol delivery as a convenient approach for repeated applications of immunostimulants in patients with lung metastases to maintain a continuous local activation of innate immune cells while suppressing polarization of tumor-infiltrating macrophages to an M2 phenotype.
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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.