IMMU-11. NONO IS A NEW ADENOVIRUS SENSOR: IMPLICATION FOR VIROTHERAPY
نویسندگان
چکیده
Abstract The median survival for GBM patients is 15 months with a five-year rate of less than 10%. Current conventional and experimental treatments, including immune checkpoint blockade, have not improved outcomes in the vast majority glioma patients. Oncolytic viruses (OVs) are designed to specifically infect lyse cancer cells elicit an anti-tumor response. In clinical trial developed by MDACC team, 20% treated oncolytic adenovirus Delta-24-RGD showed complete response longer three years (NCT00805376). Although these studies shown that robust responses can be invoked using virotherapy, molecular mechanisms underlying OV-mediated immunity remain elusive. Exposure innate sensors induces protective antiviral immunity. Using bulk RNA sequencing infected we identified main upstream regulators IFN gamma, Interferon responsive genes 3 7, STAT3. However, RNAseq unexpectedly uncovered NONO (Non-POU Domain Containing Octamer Binding) as most relevant regulator. agreement data, Protein analyses demonstrated upregulation after infection. addition, immunofluorescence confocal microscopy examination overexpression translocation nucleus upon virus We first laboratory has sensor infection, which may great significance future development viruses. Importantly, discovered network proteins upregulated activation and, finally, established changes expression level subcellular localization coincident time during infection cultured cells. Future work focused on examining immunomodulatory functions adenoviral tumors subsequent generation NONO-resistant adenovirus.
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ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.509