ArticleJournal for immunotherapy of cancer2026
Oncolytic virus OH2 induces PD-L1 upregulation via NF-κB signaling and synergizes with anti-PD-L1 therapy in prostate cancer through a targeted extracellular vesicle delivery system.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Nucleic acid aptamers: new methods for selection, target validation, molecular diagnostics and therapeutics.Signal transduction and targeted therapy · 2026Review
- Oncolytic Virotherapy and Immunogenic Cell Death: Mechanisms, Platforms, and Clinical Translation.Viruses · 2026Review
- Bridging mechanism and clinic: unlocking the full potential of oncolytic virus-based immunotherapy.Molecular cancer · 2026Review
- Combined Dihydroartemisinin and Eupatilin Suppress Prostate Cancer through AR-Associated Ferroptosis and Modulation of Macrophage-Tumor Crosstalk.Research (Washington, D.C.) · 2026Article
- Extracellular vesicle-based therapeutic strategies for spinal tumors and associated nerve damage: advances, challenges, and future directions.Frontiers in cell and developmental biology · 2026Review
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14 authors.
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Abstract
backgroundProstate cancer (PCa) is a prevalent malignancy with limited treatment options for advanced stages. Oncolytic virotherapy represents a promising immunotherapeutic approach, but its efficacy and underlying mechanisms in PCa, particularly concerning immune checkpoint regulation, remain unclear.
methodsThe antitumor effects of the oncolytic virus oncolytic herpes simplex virus type 2 (OH2) were evaluated in PCa cell lines and mouse models. Transcriptome sequencing, western blot, chromatin immunoprecipitation-sequencing-quantitative PCR, and flow cytometry were employed to investigate the mechanism of programmed death 1 ligand 1 (PD-L1) regulation. A targeted delivery system, reactive oxygen species (ROS)-responsive aptamer-conjugated anti-prostate-specific membrane antigen (PSMA) extracellular vesicles (RRA-AP-EVs), was engineered from anti-PSMA single chain variable fragment (scFv)-modified extracellular vesicles and an ROS-responsive PD-L1 blocking aptamer. OH2 was loaded via membrane extrusion, and the resulting OH2@RRA-AP-EVs were tested for targeting and therapeutic efficacy following intravenous administration.
resultsOH2 effectively killed PCa cells but simultaneously activated the IKK/I-κBα/p65 pathway, leading to PD-L1 upregulation and adaptive immune resistance. While combining OH2 with anti-PD-L1 improved outcomes, clinical translation was hindered by delivery challenges. The novel OH2@RRA-AP-EVs system demonstrated precise tumor targeting and ROS-triggered local PD-L1 blockade. Intravenous injection of OH2@RRA-AP-EVs showed superior tumor control (inhibiting tumor growth by 70% vs free OH2) and enhanced CD8+T cell infiltration and function compared with free OH2 (greater than twofold increase in intratumoral CD8+T cell infiltration along with over twofold upregulation of key effector molecules).
conclusionThis study identifies a mechanism of OH2-induced PD-L1 expression in PCa and provides a versatile, targeted delivery platform that enables effective intravenous viro-immunotherapy, overcoming key translational barriers.
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