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

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, S. Tomei

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Abstract

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-γ, TNF-α 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-γ and TNF-α 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/β-cathenin as the top downregulated pathways in the cell lines with low inducible IRF-1 activation, suggesting that a low IRF-1 inducibility recapitulates a cancer phenotype already described in literature characterised by poor prognosis.Conclusion:Our findings support the central role of IRF-1 in influencing different tumour phenotypes.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalBritish Journal of Cancer
Volume109
Issue number1
DOIs
Publication statusPublished - 9 Jul 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Murtas, D., Maric, D., De Giorgi, V., Reinboth, J., Worschech, A., Fetsch, P., Filie, A., Ascierto, M. L., Bedognetti, D., Liu, Q., Uccellini, L., Chouchane, L., Wang, E., Marincola, F. M., & Tomei, S. (2013). IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes. British Journal of Cancer, 109(1), 76-82. https://doi.org/10.1038/bjc.2013.335