Mendez Rosa, Aptsiauri Natalia, Del Campo Ana, Maleno Isabel, Cabrera Teresa, Ruiz-Cabello Francisco, Garrido Federico, Garcia-Lora Angel
Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Cancer Immunol Immunother. 2009 Sep;58(9):1507-15. doi: 10.1007/s00262-009-0701-z. Epub 2009 Apr 2.
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 .
在许多类型的恶性肿瘤中均有HLA I类和II类细胞表面表达改变的报道,这是肿瘤细胞逃避T淋巴细胞的主要机制之一。在本报告中,我们回顾了对欧洲可检索肿瘤细胞系数据库中91个人黑色素瘤细胞系的HLA I类和II类分子组成性及IFN-γ诱导表达的研究结果,并将其与已发表的其他类型癌症的HLA表达数据进行比较。在所研究的细胞系中,高比例(67%)出现了HLA I类细胞表面表达的各种改变。这些改变包括HLA I类的完全缺失到选择性缺失,与β2-微球蛋白基因突变、HLA I类基因及抗原加工机制成分的转录下调,或6号染色体杂合性缺失有关。最常观察到的表型是HLA-B位点的选择性下调,经IFN-γ处理后可逆转。在71.5%的分析细胞系中,至少一个HLA II类位点的组成性或IFN-γ诱导表面表达呈阳性。定义了四种不同的HLA II类表达表型,并讨论了I类和II类分子表达之间的正相关性。有关这些黑色素瘤细胞系HLA表达模式及其他免疫特征的更详细信息可在以下网站http://www.ebi.ac.uk/ipd/estdab上找到。