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, Davide Bedognetti, Q. Liu, L. Uccellini, Lotfi Chouchane, E. Wang, F. M. Marincola, Sara Tomei

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Fingerprint

Interferon Regulatory Factor-1
Phenotype
Neoplasms
Cell Line
Microarray Analysis
Immunotherapy
Melanoma
Down-Regulation
Cytokines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Murtas, D., Maric, D., De Giorgi, V., Reinboth, J., Worschech, A., Fetsch, P., ... 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

IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes. / Murtas, D.; Maric, D.; De Giorgi, V.; Reinboth, J.; Worschech, A.; Fetsch, P.; Filie, A.; Ascierto, M. L.; Bedognetti, Davide; Liu, Q.; Uccellini, L.; Chouchane, Lotfi; Wang, E.; Marincola, F. M.; Tomei, Sara.

In: British Journal of Cancer, Vol. 109, No. 1, 09.07.2013, p. 76-82.

Research output: Contribution to journalArticle

Murtas, D, Maric, D, De Giorgi, V, Reinboth, J, Worschech, A, Fetsch, P, Filie, A, Ascierto, ML, Bedognetti, D, Liu, Q, Uccellini, L, Chouchane, L, Wang, E, Marincola, FM & Tomei, S 2013, 'IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes', British Journal of Cancer, vol. 109, no. 1, pp. 76-82. https://doi.org/10.1038/bjc.2013.335
Murtas D, Maric D, De Giorgi V, Reinboth J, Worschech A, Fetsch P et al. IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes. British Journal of Cancer. 2013 Jul 9;109(1):76-82. https://doi.org/10.1038/bjc.2013.335
Murtas, D. ; Maric, D. ; De Giorgi, V. ; Reinboth, J. ; Worschech, A. ; Fetsch, P. ; Filie, A. ; Ascierto, M. L. ; Bedognetti, Davide ; Liu, Q. ; Uccellini, L. ; Chouchane, Lotfi ; Wang, E. ; Marincola, F. M. ; Tomei, Sara. / IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes. In: British Journal of Cancer. 2013 ; Vol. 109, No. 1. pp. 76-82.
@article{eed61298ebda43629cc8c12a29b92720,
title = "IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes",
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.",
author = "D. Murtas and D. Maric and {De Giorgi}, V. and J. Reinboth and A. Worschech and P. Fetsch and A. Filie and Ascierto, {M. L.} and Davide Bedognetti and Q. Liu and L. Uccellini and Lotfi Chouchane and E. Wang and Marincola, {F. M.} and Sara Tomei",
year = "2013",
month = "7",
day = "9",
doi = "10.1038/bjc.2013.335",
language = "English",
volume = "109",
pages = "76--82",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - IRF-1 responsiveness to IFN-γ predicts different cancer immune phenotypes

AU - Murtas, D.

AU - Maric, D.

AU - De Giorgi, V.

AU - Reinboth, J.

AU - Worschech, A.

AU - Fetsch, P.

AU - Filie, A.

AU - Ascierto, M. L.

AU - Bedognetti, Davide

AU - Liu, Q.

AU - Uccellini, L.

AU - Chouchane, Lotfi

AU - Wang, E.

AU - Marincola, F. M.

AU - Tomei, Sara

PY - 2013/7/9

Y1 - 2013/7/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84880253427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880253427&partnerID=8YFLogxK

U2 - 10.1038/bjc.2013.335

DO - 10.1038/bjc.2013.335

M3 - Article

VL - 109

SP - 76

EP - 82

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -