ArticleThe Journal of clinical investigation2009
Polyethylenimine-based siRNA nanocomplexes reprogram tumor-associated dendritic cells via TLR5 to elicit therapeutic antitumor immunity.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
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Who cites it
127 citing papers in PubMed, 207 citations in OpenAlex.
- Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes.Journal of leukocyte biology · 2013Trial
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- Nanotechnology Meets Immunotherapy: Crosstalks Against Cancer.Immunity, inflammation and disease · 2026Review
- Application of dendritic cell extracellular vesicles as a valid nanoparticle platform for cancer therapies: a narrative review.Stem cell research & therapy · 2026Review
- Ovarian cancer drives TLR5-dependent expansion of myeloid progenitors through systemic ligand dissemination.Journal of leukocyte biology · 2025Article
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- TLR5 Signaling Causes Dendritic Cell Dysfunction and Orchestrates Failure of Immune Checkpoint Therapy against Ovarian Cancer.Cancer immunology research · 2025Article
- Nanomaterials-driven in situ vaccination: a novel frontier in tumor immunotherapy.Journal of hematology & oncology · 2025Review
- siRNA as a criterion in host immunity and cancer immunotherapy: modulating factors and nano-conjugate based approach for intervention.International journal of biological sciences · 2025Review
- New insights for the development of efficient DNA vaccines.Microbial biotechnology · 2024Review
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- Nanotechnology for boosting ovarian cancer immunotherapy.Journal of ovarian research · 2024Review
- Non-Coding RNA in Tumor Cells and Tumor-Associated Myeloid Cells-Function and Therapeutic Potential.International journal of molecular sciences · 2024Review
- Sulfonium-Stapled Peptides-Based Neoantigen Delivery System for Personalized Tumor Immunotherapy and Prevention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- mRNA Vaccine Nanoplatforms and Innate Immunity.Viruses · 2024Review
- Transgelin 2 guards T cell lipid metabolic programming and anti-tumor function.Research square · 2023Article
- Transcriptional Targeting of Dendritic Cells Using an Optimized HumanInternational journal of molecular sciences · 2023Article
- A single local delivery of paclitaxel and nucleic acids via an immunoactive polymer eliminates tumors and induces antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Recent advances in development of nano-carriers for immunogene therapy in various complex disorders.Iranian journal of basic medical sciences · 2022Review
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The success of clinically relevant immunotherapies requires reversing tumor-induced immunosuppression. Here we demonstrated that linear polyethylenimine-based (PEI-based) nanoparticles encapsulating siRNA were preferentially and avidly engulfed by regulatory DCs expressing CD11c and programmed cell death 1-ligand 1 (PD-L1) at ovarian cancer locations in mice. PEI-siRNA uptake transformed these DCs from immunosuppressive cells to efficient antigen-presenting cells that activated tumor-reactive lymphocytes and exerted direct tumoricidal activity, both in vivo and in situ. PEI triggered robust and selective TLR5 activation in vitro and elicited the production of hallmark TLR5-inducible cytokines in WT mice, but not in Tlr5-/- littermates. Thus, PEI is a TLR5 agonist that, to our knowledge, was not previously recognized. In addition, PEI-complexed nontargeting siRNA oligonucleotides stimulated TLR3 and TLR7. The nonspecific activation of multiple TLRs (specifically, TLR5 and TLR7) reversed the tolerogenic phenotype of human and mouse ovarian tumor-associated DCs. In ovarian carcinoma-bearing mice, this induced T cell-mediated tumor regression and prolonged survival in a manner dependent upon myeloid differentiation primary response gene 88 (MyD88; i.e., independent of TLR3). Furthermore, gene-specific siRNA-PEI nanocomplexes that silenced immunosuppressive molecules on mouse tumor-associated DCs elicited discernibly superior antitumor immunity and enhanced therapeutic effects compared with nontargeting siRNA-PEI nanocomplexes. Our results demonstrate that the intrinsic TLR5 and TLR7 stimulation of siRNA-PEI nanoparticles synergizes with the gene-specific silencing activity of siRNA to transform tumor-infiltrating regulatory DCs into DCs capable of promoting therapeutic antitumor immunity.
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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.