HLA and melanoma: multiple alterations in HLA class I and II expression in human melanoma cell lines from ESTDAB cell bank

Abstract

Altered HLA class I and class II cell surface expression has been reported in many types of malignancy and represents one of the major mechanism by which tumour cells escape from T lymphocytes. In this report, we review the results obtained from the study of constitutive and IFN-gamma-induced expression of HLA class I and II molecules in 91 human melanoma cell lines from the European Searchable Tumour Cell Line Database, and compare them with published data on HLA expression in other types of cancer. Various types of alterations in HLA class I cell surface expression were found in a high percentage (67%) of the studied cell lines. These alterations range from total to selective HLA class I loss and are associated with beta2-microglobulin gene mutations, transcriptional downregulation of HLA class I genes and antigen processing machinery components, or with the loss of heterozygosity in chromosome 6. The most frequently observed phenotype is selective downregulation of HLA-B locus, reversible after treatment with IFN-gamma. The expression of constitutive- or IFN-gamma induced-surface expression of at least one HLA class II locus is positive in 71.5% of the analysed cell lines. Four different HLA class II expression phenotypes were defined, and a positive correlation between the expression of class I and II molecules is discussed. More detailed information on the HLA expression patterns and others immunological characteristics of these melanoma cell lines can be found on the following website http://www.ebi.ac.uk/ipd/estdab .

Fig. 1

Distribution of HLA class I phenotypes in 91 human melanoma cell lines (ESTDAB) and in different solid tumours. These tumours include melanoma [19], bladder cancer [30], colorectal carcinoma [29], laryngeal [28] and cervical cancer [22]. The following HLA class I expression phenotypes are compared: total loss or downregulation of HLA class I (Phenotype I); haplotype loss (Phenotype II); locus downregulation (Phenotype III); allelic loss (Phenotype IV), compound phenotype (Phenotype V); resistance to stimulation with IFN-gamma (Phenotype VI). Surface expression of HLA class I molecules in ESTDAB melanoma cell lines was determined by flow cytometry (mean fluorescence intensity, MFI) using anti-HLA class I specific antibodies. To analyse induction with IFN-gamma the melanoma cells were treated with 800 U/ml for 48 h

Fig. 2

Distribution of HLA class II phenotypes in 42 human melanoma cell lines (ESTDAB). Phenotypes 1–4 representing various patterns of HLA class II expression on the studied melanoma cell lines are presented. Surface expression of HLA class II molecules was determined by flow cytometry (mean fluorescence intensity, MFI) using a panel of HLA class II specific antibodies. To analyse induction with IFN-gamma the melanoma cells were treated with 800 U/ml for 48 h