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Characterization of HLA class I altered phenotypes in a panel of human melanoma cell lines

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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.

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Acknowledgments

This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS), Red Genomica del Cancer (C03/10), Consejeria de Salud, Plan Andaluz de Investigacion, Servicio Andaluz de Salud (SAS) in Spain, from the ESTDAB project (contract no. QLRI-CT-2001-01325), and from the European Network for the identification and validation of Antigens and biomarkers in Cancer and their application in clinical Tumor immunology (ENACT, contract No. 503306).

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Correspondence to Federico Garrido.

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Rosa Méndez and Teresa Rodríguez have equally contributed to this work and both should be considered as first authors.

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Méndez, R., Rodríguez, T., Del Campo, A. et al. Characterization of HLA class I altered phenotypes in a panel of human melanoma cell lines. Cancer Immunol Immunother 57, 719–729 (2008). https://doi.org/10.1007/s00262-007-0411-3

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  • DOI: https://doi.org/10.1007/s00262-007-0411-3

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