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IRF-1 responsiveness to IFN-c predicts different cancer immune phenotypes

By D Murtas, D Maric, V De Giorgi, J Reinboth, A Worschech, P Fetsch, A Filie, M L Ascierto, D Bedognetti, Q Liu, L Uccellini, L Chouchane, E Wang, F M Marincola and S Tomei


Background: Several lines of evidence suggest a dichotomy between immune active and quiescent cancers, with the former associated with a good prognostic phenotype and better responsiveness to immunotherapy. Central to such dichotomy is the master regulator of the acute inflammatory process interferon regulatory factor (IRF)-1. However, it remains unknown whether the responsiveness of IRF-1 to cytokines is able to differentiate cancer immune phenotypes. Methods: IRF-1 activation was measured in 15 melanoma cell lines at basal level and after treatment with IFN-g, TNF-a and a combination of both. Microarray analysis was used to compare transcriptional patterns between cell lines characterised by high or low IRF-1 activation. Results: We observed a strong positive correlation between IRF-1 activation at basal level and after IFN-g and TNF-a treatment. Microarray demonstrated that three cell lines with low and three with high IRF-1 inducible translocation scores differed in the expression of 597 transcripts. Functional interpretation analysis showed mTOR and Wnt/b-cathenin as the top downregulate

Year: 2016
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