IRF5 gene polymorphisms in melanoma

Lorenzo Uccellini, Valeria De Giorgi, Yingdong Zhao, Barbara Tumaini, Narnygerel Erdenebileg, Mark E. Dudley, Sara Tomei, Davide Bedognetti, Maria L. Ascierto, Qiuzhen Liu, Richard Simon, Leah Kottyan, Kenneth M. Kaufman, John B. Harley, Ena Wang, Steven A. Rosenberg, Francesco M. Marincola

Research output: Contribution to journalArticle

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Abstract

Background: Interferon regulatory factor (IRF)-5 is a transcription factor involved in type I interferon signaling whose germ line variants have been associated with autoimmune pathogenesis. Since relationships have been observed between development of autoimmunity and responsiveness of melanoma to several types of immunotherapy, we tested whether polymorphisms of IRF5 are associated with responsiveness of melanoma to adoptive therapy with tumor infiltrating lymphocytes (TILs).Methods: 140 TILs were genotyped for four single nucleotide polymorphisms (rs10954213, rs11770589, rs6953165, rs2004640) and one insertion-deletion in the IRF5 gene by sequencing. Gene-expression profile of the TILs, 112 parental melanoma metastases (MM) and 9 cell lines derived from some metastases were assessed by Affymetrix Human Gene ST 1.0 array.Results: Lack of A allele in rs10954213 (G > A) was associated with non-response (p < 0.005). Other polymorphisms in strong linkage disequilibrium with rs10954213 demonstrated similar trends. Genes differentially expressed in vitro between cell lines carrying or not the A allele could be applied to the transcriptional profile of 112 melanoma metastases to predict their responsiveness to therapy, suggesting that IRF5 genotype may influence immune responsiveness by affecting the intrinsic biology of melanoma.Conclusions: This study is the first to analyze associations between melanoma immune responsiveness and IRF5 polymorphism. The results support a common genetic basis which may underline the development of autoimmunity and melanoma immune responsiveness.

Original languageEnglish
Article number170
JournalJournal of Translational Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - 21 Aug 2012
Externally publishedYes

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Polymorphism
Lymphocytes
Melanoma
Genes
Tumors
Tumor-Infiltrating Lymphocytes
Interferon Regulatory Factors
Cells
Interferon Type I
Neoplasm Metastasis
Autoimmunity
Gene expression
Alleles
Transcription Factors
Nucleotides
Cell Line
Linkage Disequilibrium
Transcriptome
Germ Cells
Immunotherapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Uccellini, L., De Giorgi, V., Zhao, Y., Tumaini, B., Erdenebileg, N., Dudley, M. E., ... Marincola, F. M. (2012). IRF5 gene polymorphisms in melanoma. Journal of Translational Medicine, 10(1), [170]. https://doi.org/10.1186/1479-5876-10-170

IRF5 gene polymorphisms in melanoma. / Uccellini, Lorenzo; De Giorgi, Valeria; Zhao, Yingdong; Tumaini, Barbara; Erdenebileg, Narnygerel; Dudley, Mark E.; Tomei, Sara; Bedognetti, Davide; Ascierto, Maria L.; Liu, Qiuzhen; Simon, Richard; Kottyan, Leah; Kaufman, Kenneth M.; Harley, John B.; Wang, Ena; Rosenberg, Steven A.; Marincola, Francesco M.

In: Journal of Translational Medicine, Vol. 10, No. 1, 170, 21.08.2012.

Research output: Contribution to journalArticle

Uccellini, L, De Giorgi, V, Zhao, Y, Tumaini, B, Erdenebileg, N, Dudley, ME, Tomei, S, Bedognetti, D, Ascierto, ML, Liu, Q, Simon, R, Kottyan, L, Kaufman, KM, Harley, JB, Wang, E, Rosenberg, SA & Marincola, FM 2012, 'IRF5 gene polymorphisms in melanoma', Journal of Translational Medicine, vol. 10, no. 1, 170. https://doi.org/10.1186/1479-5876-10-170
Uccellini L, De Giorgi V, Zhao Y, Tumaini B, Erdenebileg N, Dudley ME et al. IRF5 gene polymorphisms in melanoma. Journal of Translational Medicine. 2012 Aug 21;10(1). 170. https://doi.org/10.1186/1479-5876-10-170
Uccellini, Lorenzo ; De Giorgi, Valeria ; Zhao, Yingdong ; Tumaini, Barbara ; Erdenebileg, Narnygerel ; Dudley, Mark E. ; Tomei, Sara ; Bedognetti, Davide ; Ascierto, Maria L. ; Liu, Qiuzhen ; Simon, Richard ; Kottyan, Leah ; Kaufman, Kenneth M. ; Harley, John B. ; Wang, Ena ; Rosenberg, Steven A. ; Marincola, Francesco M. / IRF5 gene polymorphisms in melanoma. In: Journal of Translational Medicine. 2012 ; Vol. 10, No. 1.
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AU - Uccellini, Lorenzo

AU - De Giorgi, Valeria

AU - Zhao, Yingdong

AU - Tumaini, Barbara

AU - Erdenebileg, Narnygerel

AU - Dudley, Mark E.

AU - Tomei, Sara

AU - Bedognetti, Davide

AU - Ascierto, Maria L.

AU - Liu, Qiuzhen

AU - Simon, Richard

AU - Kottyan, Leah

AU - Kaufman, Kenneth M.

AU - Harley, John B.

AU - Wang, Ena

AU - Rosenberg, Steven A.

AU - Marincola, Francesco M.

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N2 - Background: Interferon regulatory factor (IRF)-5 is a transcription factor involved in type I interferon signaling whose germ line variants have been associated with autoimmune pathogenesis. Since relationships have been observed between development of autoimmunity and responsiveness of melanoma to several types of immunotherapy, we tested whether polymorphisms of IRF5 are associated with responsiveness of melanoma to adoptive therapy with tumor infiltrating lymphocytes (TILs).Methods: 140 TILs were genotyped for four single nucleotide polymorphisms (rs10954213, rs11770589, rs6953165, rs2004640) and one insertion-deletion in the IRF5 gene by sequencing. Gene-expression profile of the TILs, 112 parental melanoma metastases (MM) and 9 cell lines derived from some metastases were assessed by Affymetrix Human Gene ST 1.0 array.Results: Lack of A allele in rs10954213 (G > A) was associated with non-response (p < 0.005). Other polymorphisms in strong linkage disequilibrium with rs10954213 demonstrated similar trends. Genes differentially expressed in vitro between cell lines carrying or not the A allele could be applied to the transcriptional profile of 112 melanoma metastases to predict their responsiveness to therapy, suggesting that IRF5 genotype may influence immune responsiveness by affecting the intrinsic biology of melanoma.Conclusions: This study is the first to analyze associations between melanoma immune responsiveness and IRF5 polymorphism. The results support a common genetic basis which may underline the development of autoimmunity and melanoma immune responsiveness.

AB - Background: Interferon regulatory factor (IRF)-5 is a transcription factor involved in type I interferon signaling whose germ line variants have been associated with autoimmune pathogenesis. Since relationships have been observed between development of autoimmunity and responsiveness of melanoma to several types of immunotherapy, we tested whether polymorphisms of IRF5 are associated with responsiveness of melanoma to adoptive therapy with tumor infiltrating lymphocytes (TILs).Methods: 140 TILs were genotyped for four single nucleotide polymorphisms (rs10954213, rs11770589, rs6953165, rs2004640) and one insertion-deletion in the IRF5 gene by sequencing. Gene-expression profile of the TILs, 112 parental melanoma metastases (MM) and 9 cell lines derived from some metastases were assessed by Affymetrix Human Gene ST 1.0 array.Results: Lack of A allele in rs10954213 (G > A) was associated with non-response (p < 0.005). Other polymorphisms in strong linkage disequilibrium with rs10954213 demonstrated similar trends. Genes differentially expressed in vitro between cell lines carrying or not the A allele could be applied to the transcriptional profile of 112 melanoma metastases to predict their responsiveness to therapy, suggesting that IRF5 genotype may influence immune responsiveness by affecting the intrinsic biology of melanoma.Conclusions: This study is the first to analyze associations between melanoma immune responsiveness and IRF5 polymorphism. The results support a common genetic basis which may underline the development of autoimmunity and melanoma immune responsiveness.

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