ArticleJournal for immunotherapy of cancer2021
Intratumoral combination therapy with poly(I:C) and resiquimod synergistically triggers tumor-associated macrophages for effective systemic antitumoral immunity.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 84 citations in OpenAlex.
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- Cancer immunotherapy targeting murine myeloid cells requires endosomal pattern recognition.Nature communications · 2026Article
- Chenodeoxycholic acid restrains tumor growth via TGR5-dependent type 1 dendritic cells cross-priming.Signal transduction and targeted therapy · 2026Article
- Radiopaque microsphere-hydrogel composite for extended-release intratumoral immunotherapy in a large animal model.Drug delivery and translational research · 2026Article
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- Tumour-resident oncolytic bacteria trigger potent anticancer effects through selective intratumoural thrombosis and necrosis.Nature biomedical engineering · 2026Article
- Multi-omics analysis identifies TLRscore for prognostic prediction and highlights TLR8 in macrophage-mediated antitumor immunity of lung adenocarcinoma.Frontiers in immunology · 2026Article
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- Poly(I:C) and R848 adjuvants elicit sizeable humoral immunity to liver stage malaria antigens.Frontiers in immunology · 2026Article
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- Norcantharidin promotes M1 macrophage polarization and suppresses colorectal cancer growth.Acta pharmacologica Sinica · 2025Article
- Emerging therapeutics targeting tumor-associated macrophages for the treatment of solid organ cancers.Expert opinion on emerging drugs · 2025Review
- Novel immune drug combination induces tumour microenvironment remodelling and reduces the dosage of anti-PD-1 antibody.Scientific reports · 2025Article
- Tp53 determines the spatial dynamics of M1/M2 tumor-associated macrophages and M1-driven tumoricidal effects.Cell death & disease · 2025Article
- Intratumoral injection of R848 and poly(I:C) synergistically promoted antitumor immune responses by reprogramming macrophage polarization and activating DCs in lung cancer.Clinical and experimental immunology · 2025Article
- New horizons in cancer immunotherapy: The evolving role of R848 and R837 (Review).Molecular and clinical oncology · 2025Review
- Intratumoral sustained release of resiquimod with ablative fractional laser induces efficacy in a cutaneous squamous cell carcinoma mouse model.Frontiers in immunology · 2025Article
- Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.Molecular and cellular biochemistry · 2025Article
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor-associated macrophages (TAMs) play a key immunosuppressive role that limits the ability of the immune system to fight cancer and hinder the antitumoral efficacy of most treatments currently applied in the clinic. Previous studies have evaluated the antitumoral immune response triggered by (TLR) agonists, such as poly(I:C), imiquimod (R837) or resiquimod (R848) as monotherapies; however, their combination for the treatment of cancer has not been explored. This study investigates the antitumoral efficacy and the macrophage reprogramming triggered by poly(I:C) combined with R848 or with R837, versus single treatments.
methodsTLR agonist treatments were evaluated in vitro for toxicity and immunostimulatory activity by Alamar Blue, ELISA and flow cytometry using primary human and murine M-CSF-differentiated macrophages. Cytotoxic activity of TLR-treated macrophages toward cancer cells was evaluated with an in vitro functional assay by flow cytometry. For in vivo experiments, the CMT167 lung cancer model and the MN/MCA1 fibrosarcoma model metastasizing to lungs were used; tumor-infiltrating leukocytes were evaluated by flow cytometry, RT-qPCR, multispectral immunophenotyping, quantitative proteomic experiments, and protein-protein interaction analysis.
resultsResults demonstrated the higher efficacy of poly(I:C) combined with R848 versus single treatments or combined with R837 to polarize macrophages toward M1-like antitumor effectors in vitro. In vivo, the intratumoral synergistic combination of poly(I:C)+R848 significantly prevented tumor growth and metastasis in lung cancer and fibrosarcoma immunocompetent murine models. Regressing tumors showed increased infiltration of macrophages with a higher M1:M2 ratio, recruitment of CD4 DISCUSSION: These findings demonstrate the antitumor immune responses mediated by macrophage activation on local administration of poly(I:C)+R848 combination and support the intratumoral application of this therapy to patients with solid tumors in the clinic.
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