ArticleJournal for immunotherapy of cancer2019
TLR9 activation cooperates with T cell checkpoint blockade to regress poorly immunogenic melanoma.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Pooled it
- Tilsotolimod with Ipilimumab Drives Tumor Responses in Anti-PD-1 Refractory Melanoma.Cancer discovery · 2021Trial
- Ultrasound medicine in the era of precision theranostics: Mechanisms, molecular strategies, and clinical translation.Iranian journal of basic medical sciences · 2026Review
- New Standards in the Treatment of Advanced Metastatic Melanoma: Immunotherapy and BRAF-Targeted Therapies as Emerging Paradigms.Current pharmaceutical design · 2026Review
- CD40 agonist improves the therapeutic efficacy of irreversible electroporation ablation for metastatic melanoma by promoting unexpected CD8Cancer immunology, immunotherapy : CII · 2025Article
- Lefitolimod in Combination with Ipilimumab in Patients with Advanced Solid Tumors: A Phase I Trial.Journal of immunotherapy and precision oncology · 2025Article
- Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms.Cancer communications (London, England) · 2025Review
- Local CpG-Molecular therapy. Nucleic acids · 2024Article
- Targeting of TAMs: can we be more clever than cancer cells?Cellular & molecular immunology · 2024Review
- Plasmacytoid Dendritic Cells Mediate CpG-ODN-induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis.Nature communications · 2024Article
- Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease.Journal for immunotherapy of cancer · 2024Article
- 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
- Nano-Regulator Inhibits Tumor Immune Escape via the "Two-Way Regulation" Epigenetic Therapy Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PD-1 blockade in combination with dasatinib potentiates induction of anti-acute lymphocytic leukemia immunity.Journal for immunotherapy of cancer · 2023Article
- Enhanced systemic tumor suppression by in situ vaccine combining radiation and OX40 agonist with CpG therapy.Journal of translational medicine · 2023Article
- Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model.Vaccines · 2023Article
- Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma.Cancer immunology, immunotherapy : CII · 2023Article
- Neutrophils in Cancer and Potential Therapeutic Strategies Using Neutrophil-Derived Exosomes.Vaccines · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tumors that lack pre-existing immune infiltration respond poorly to T cell checkpoint blockade immunotherapy. These cancers often surround themselves with high densities of suppressive myeloid stroma while excluding immunostimulatory dendritic cells. Tumor-resident myeloid cells and selected lymphocyte populations retain expression of Toll-like Receptors (TLR) that sense common features of pathogens and activate innate immunity in response. We explored whether agonists of TLR9 could augment innate immunity to promote tumor regression alone or in combination with T cell checkpoint blockade. In the setting of the immunogenic B16-Ova (Ovalbumin) expressing melanoma model, local injection of the CpG oligonucleotide TLR9 agonist ODN1826 combined with systemic CTLA-4 blockade cured 45% of mice of both their treated and an untreated tumor on the opposite flank demonstrating the synergistic potential of this combination. Next, in the non-immunogenic B16-F10 melanoma model, we showed that only intra-tumoral, but not systemic TLR9 activation augments the therapeutic potential of checkpoint blockade. In this setting, intra-tumoral TLR9 activation cooperated equally with either CTLA-4 or PD-1 blockade co-administered locally or given systemically; however, the uninjected tumor rarely regressed. Anti-CTLA-4 combinations were associated with improved intra-tumoral CD8 to regulatory T cell ratios, while anti-PD-1 combinations elicited improved ratios of CD8 T cells relative to suppressive myeloid stroma. Using both a TLR9 agonist (MGN1703) and a CTLA-4 antibody (9D9-IgG2a) of increased potency cured 50% of bi-lateral B16-F10 melanoma. These findings suggest that intra-tumoral TLR9 agonists can improve sensitivity of poorly immunogenic tumors to T cell checkpoint blockade, and that newer, higher potency TLR agonists and checkpoint antibodies can raise the therapeutic ceiling for this combination therapy.
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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.