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Characterization of HLA class I altered phenotypes in a panel of human melanoma cell lines
Authors:Rosa Méndez  Teresa Rodríguez  Ana Del Campo  Eva Monge  Isabel Maleno  Natalia Aptsiauri  Pilar Jiménez  Susana Pedrinaci  Graham Pawelec  Francisco Ruiz-Cabello  Federico Garrido
Institution:(1) Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avd. Fuerzas Armadas 2, 18014 Granada, Spain;(2) Center for Medical Research, University of Tübingen Clinical School, Tübingen, Germany
Abstract:Background Altered HLA class I cell surface expression is one of the major mechanisms by which tumor cells escape from T lymphocytes. Immunohistochemistry-defined phenotypes of lost HLA class I expression have been described in human solid tumors, nut less information is available on melanoma cell lines. Objectives To describe the frequency and distribution of different types of HLA class I antigen alterations in 91 melanoma cell lines from the European Searchable Tumour Cell and Databank (ESTDAB). Methods The HLA class I expression was assessed by flow cytometry and HLA genotyping. Results We found various types of HLA class I cell surface alterations in about 67% of the melanoma cell lines. These alterations range from total to selective HLA class I loss due to loss of heterozygosity (LOH), haplotype loss, β2-microglobulin gene mutation, and/or total or selective down-regulation of HLA class I molecules. The most frequently observed phenotype is down-regulation of HLA-B locus that was reversible after treatment with IFN -γ. Conclusions In general, HLA class I alterations in the majority of the cells analyzed were of regulatory nature and could be restored by IFN-γ. Analysis of the frequency of distinct HLA class I altered phenotypes in these melanoma cell lines revealed specific differences compared to other types of tumors. Rosa Méndez and Teresa Rodríguez have equally contributed to this work and both should be considered as first authors.
Keywords:HLA class I  Altered phenotypes  Melanoma
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