IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes. Academic Article uri icon

Overview

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.

publication date

  • June 27, 2013

Research

keywords

  • Interferon Regulatory Factor-1
  • Interferon-gamma
  • Melanoma

Identity

PubMed Central ID

  • PMC3708578

Scopus Document Identifier

  • 84880253427

Digital Object Identifier (DOI)

  • 10.1038/bjc.2013.335

PubMed ID

  • 23807161

Additional Document Info

volume

  • 109

issue

  • 1