ArticleJournal for immunotherapy of cancer2024
Combining toll-like receptor agonists with immune checkpoint blockade affects antitumor vaccine efficacy.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mapping research trends in macrophage polarization and immunotherapeutic potential in prostate cancer: a bibliometric and visual analysis.Frontiers in oncology · 2026Pooled it
- Sequential nanocatalytic therapy and lysosomal dysfunction for overcoming castration-resistant prostate cancer.Bioactive materials · 2026Article
- CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance.Cancer immunology research · 2026Article
- Leveraging Macrophage Metabolic Reprogramming for Enhanced Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Antigen cross-presentation potentiating cancer vaccine adjuvant for T cell expansion and synergy with anti-PD-1.NPJ vaccines · 2026Article
- Advances in molecular innate immune regulation in the development and therapeutic strategies of allergic rhinitis vaccines.Frontiers in immunology · 2026Review
- Toll like receptor agonist effects on human CD8+ T cell activation and expression of T cell checkpoint receptors.Human vaccines & immunotherapeutics · 2025Article
- β-amino acid substitution in the SIINFEKL antigen alters immunological recognition.Cancer biology & therapy · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Phosphorylated Toll-like receptor 3 nuclear translocation in cancer cell promotes metastasis and chemoresistance.Signal transduction and targeted therapy · 2025Article
- A comprehensive insights of cancer immunotherapy resistance.Medical oncology (Northwood, London, England) · 2025Review
- Leveraging mRNA technology for antigen based immuno-oncology therapies.Journal for immunotherapy of cancer · 2025Review
- Peptides as Versatile Regulators in Cancer Immunotherapy: Recent Advances, Challenges, and Future Prospects.Pharmaceutics · 2025Review
- Nanovaccines empowering CD8Theranostics · 2025Review
- Leveraging innate immune signals in CD8+ T cells to boost antitumor immunity.Frontiers in immunology · 2025Review
- The 41BB-agonist potentiates the therapeutic efficacy of a combined irreversible electroporation ablation treatment of lung cancer by promoting unexpected CD8Frontiers in immunology · 2025Article
- Unleashing the power of peptides in prostate cancer immunotherapy: mechanism, facts and perspectives.Frontiers in pharmacology · 2025Review
- Navigating the role of protein lactylation in prostate cancer and its implications for immunotherapy.Journal of Cancer · 2025Review
- COPD and Immune Checkpoint Inhibitors for Cancer: A Literature Review.International journal of chronic obstructive pulmonary disease · 2024Review
Corrections and comments
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Authors and funding
4 authors.
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Abstract
backgroundT cell checkpoint receptors are expressed when T cells are activated, and modulation of the expression or signaling of these receptors can alter the function of T cells and their antitumor efficacy. We previously found that T cells activated with cognate antigen had increases in the expression of PD-1, and this was attenuated in the presence of multiple toll-like receptor (TLR) agonists, notably TLR3 plus TLR9. In the current report, we sought to investigate whether combining TLR agonists with immune checkpoint blockade can further augment vaccine-mediated T cell antitumor immunity in murine tumor models.
methodsTLR agonists (TLR3 plus TLR9) and immune checkpoint inhibitors (antibodies targeting PD-1, CTLA-4, LAG-3, TIM-3 or VISTA) were combined and delivered with vaccines or vaccine-activated CD8+T cells to E.G7-OVA or MyC-CaP tumor-bearing mice. Tumors were assessed for growth and then collected and analyzed by flow cytometry.
resultsImmunization of E.G7-OVA tumor-bearing mice with SIINFEKL peptide vaccine, coadministered with TLR agonists and αCTLA-4, demonstrated greater antitumor efficacy than immunization with TLR agonists or αCTLA-4 alone. Conversely, the antitumor efficacy was abrogated when vaccine and TLR agonists were combined with αPD-1. TLR agonists suppressed PD-1 expression on regulatory T cells (Tregs) and activated this population. Depletion of Tregs in tumor-bearing mice led to greater antitumor efficacy of this combination therapy, even in the presence of αPD-1. Combining vaccination with TLR agonists and αCTLA-4 or αLAG-3 showed greater antitumor than with combinations with αTIM-3 or αVISTA.
conclusionThe combination of TLR agonists and αCTLA-4 or αLAG-3 can further improve the efficacy of a cancer vaccine, an effect not observed using αPD-1 due to activation of Tregs when αPD-1 was combined with TLR3 and TLR9 agonists. These data suggest that optimal combinations of TLR agonists and immune checkpoint blockade may improve the efficacy of human anticancer vaccines.
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