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- W4366185736 abstract "Oncolytic virotherapy represents a new approach in the treatment of metastatic melanoma. The efficacy of this therapeutic approach is limited by the release of type I IFNs in the tumor microenvironment that can induce an antiviral state in tumor cells. Here we investigated the ability of type I IFNs to impair oncolytic virolysis in a panel of human melanoma cell lines. We found that human melanoma cells with a dedifferentiated phenotype showed increased type I IFN mediated resistance against viral oncolysis. Interestingly, IFN-responsive dedifferentiated melanoma cells constitutively expressed an interferon-related DNA damage signature (IRDS) that was previously described in tumor cells that resisted radio- and chemo-therapy. Using a doxycycline-inducible gene expression system we observed that induction of the melanocyte lineage transcription factor MITF decreased IFN-mediated resistance against viral oncolysis. Transcriptome analyses revealed that experimental MITF activation modulates the IFN-induced transcriptional network leading to decreased expression of IRDS genes. Taken together our results imply that the acquisition of a dedifferentiated MITF-low melanoma cell state limits the efficacy of oncolytic virotherapy through increased IFN-responsiveness." @default.
- W4366185736 created "2023-04-19" @default.
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- W4366185736 date "2023-05-01" @default.
- W4366185736 modified "2023-09-28" @default.
- W4366185736 title "1252 Interferon mediated resistance of melanoma cells to oncolytic viruses is regulated by the melanocyte lineage transcription factor MITF" @default.
- W4366185736 doi "https://doi.org/10.1016/j.jid.2023.03.1266" @default.
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