ArticleScientific reports2021
A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Inverse Regulation of TLR4 and PD-L1 Shapes the Inflammatory Tumor Microenvironment in Oral Squamous Cell Carcinomas.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025Article
- Gut commensal Bifidobacterium-derived extracellular vesicles modulate the therapeutic effects of anti-PD-1 in lung cancer.Nature communications · 2025Article
- Radiotherapy Combined with Intralesional Immunostimulatory Agents for Soft Tissue Sarcomas.Seminars in radiation oncology · 2024Review
- Quantifying the impact of immunotherapy on RNA dynamics in cancer.Journal for immunotherapy of cancer · 2023Article
- NOD-scid IL2rγnull mice lacking TLR4 support human immune system development and the study of human-specific innate immunity.Journal of leukocyte biology · 2023Article
- Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery.Frontiers in oncology · 2023Review
- Lenvatinib Induces Immunogenic Cell Death and Triggers Toll-Like Receptor-3/4 Ligands in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Article
- Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives.Frontiers in immunology · 2023Review
- Article
- Transcriptome Analysis of Tumor-Infiltrating Lymphocytes Identifies NK Cell Gene Signatures Associated With Lymphocyte Infiltration and Survival in Soft Tissue Sarcomas.Frontiers in immunology · 2022Article
- Engineering Therapeutic Strategies in Cancer Immunotherapy via Exogenous Delivery of Toll-like Receptor Agonists.Pharmaceutics · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.
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