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IRF5 gene polymorphisms in melanoma

Authors :
Maria Libera Ascierto
Sara Tomei
Leah C. Kottyan
Barbara Tumaini
Kenneth M. Kaufman
Yingdong Zhao
Steven A. Rosenberg
John B. Harley
Mark E. Dudley
Lorenzo Uccellini
Davide Bedognetti
Richard Simon
Francesco M. Marincola
Ena Wang
Narnygerel Erdenebileg
Qiuzhen Liu
Valeria De Giorgi
Source :
Journal of Translational Medicine, Journal of Translational Medicine, Vol 10, Iss 1, p 170 (2012)
Publication Year :
2012
Publisher :
BioMed Central, 2012.

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 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.

Details

Language :
English
ISSN :
14795876
Volume :
10
Database :
OpenAIRE
Journal :
Journal of Translational Medicine
Accession number :
edsair.doi.dedup.....8a551e9701331ed4cb5a429ebfbc4f66