ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
RNAi mediated silencing of STAT3/PD-L1 in tumor-associated immune cells induces robust anti-tumor effects in immunotherapy resistant tumors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- siRNA-mediated silencing of placenta-specific protein 1 (PLAC1) alters CD4+, CD8+, and regulatory T cells in a murine colon cancer model.Scientific reports · 2026Article
- Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting.ACS applied materials & interfaces · 2026Article
- Synergistic Mn-MOF Activation of Pistol Ribozymes for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ODF3B Promotes the Progression of Clear Cell Renal Cell Carcinoma via the JAK/STAT Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- Engineered lipid hybrid nanoparticles for targeted delivery of SH2 superbinder and breast cancer therapy.Journal of nanobiotechnology · 2026Article
- NF-κB and STAT3 signaling uniquely stratify survival in female glioblastoma patients.iScience · 2026Article
- Emerging nano-immunotherapeutic strategies achieve metastatic colorectal cancer precision therapy.Journal of nanobiotechnology · 2026Review
- The metabolic environment within solid tumors drives a complex crosstalk between macrophages and NK cells.Frontiers in immunology · 2026Review
- Nanoformulated Phytochemicals Against Pancreatic Cancer: Emerging Advances in Therapeutic Strategies.International journal of nanomedicine · 2026Review
- Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.Frontiers in immunology · 2026Review
- Reshaping tumor immune microenvironment through ROS-responsive prodrug polyplexes via synergistic effect of CRISPRi system and epigenetic inhibitor for breast cancer therapy.Materials today. Bio · 2025Article
- STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- New insights into the role of IFN-α/β and TLR7/8/9 in cancer immunotherapy and systemic autoimmunity.Journal for immunotherapy of cancer · 2025Review
- Targeting tumor immune evasion: the role of PD-L1 siRNA in advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- Albumin-binding dendritic siRNA improves delivery and efficacy to solid tumors in a melanoma model.Molecular therapy. Nucleic acids · 2025Article
- Article
- siRNA tackles cancer: Immune checkpoint inhibitors and siRNA combinations.Molecular therapy. Nucleic acids · 2025Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant tumors are often associated with an immunosuppressive tumor microenvironment (TME), rendering most of them resistant to standard-of-care immune checkpoint inhibitors (CPIs). Signal transducer and activator of transcription 3 (STAT3), a ubiquitously expressed transcription factor, has well-defined immunosuppressive functions in several leukocyte populations within the TME. Since the STAT3 protein has been challenging to target using conventional pharmaceutical modalities, we investigated the feasibility of applying systemically delivered RNA interference (RNAi) agents to silence its mRNA directly in tumor-associated immune cells. In preclinical rodent tumor models, chemically stabilized acylated small interfering RNAs (siRNAs) selectively silenced Stat3 mRNA in multiple relevant cell types, reduced STAT3 protein levels, and increased cytotoxic T cell infiltration. In a murine model of CPI-resistant pancreatic cancer, RNAi-mediated Stat3 silencing resulted in tumor growth inhibition, which was further enhanced in combination with CPIs. To further exemplify the utility of RNAi for cancer immunotherapy, this technology was used to silence Cd274, the gene encoding the immune checkpoint protein programmed death-ligand 1 (PD-L1). Interestingly, silencing of Cd274 was effective in tumor models that are resistant to PD-L1 antibody therapy. These data represent the first demonstration of systemic delivery of RNAi agents to the TME and suggest applying this technology for immuno-oncology applications.
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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.