Levy Estrella Mariel, Bianchini Michele, Von Euw Erika María, Barrio Maria Marcela, Bravo Alicia Inés, Furman David, Domenichini Enzo, Macagno Carlos, Pinsky Victor, Zucchini Cinzia, Valvassori Luisa, Mordoh José
Centro de Investigaciones Oncológicas (CIO-FUCA), Buenos Aires, Argentina.
Int J Oncol. 2008 Mar;32(3):633-41.
HLA-E is a non-classical MHC molecule whose expression by tumour cells has been recently reported in several human cancer types. We studied HLA-E expression in colorectal cancer patients, its clinical significance and prognostic value, as well as characterized its expression in colorectal cancer cell lines. We analysed HLA-E expression at the transcript level by qRT-PCR in micro-dissected samples and at the protein level by semiquantitative immunohistochemistry on paraffin-embedded tissue sections from 42 biopsies of colorectal cancer patients. We observed that HLA-E transcript and protein are spontaneously overexpressed in a significant proportion of colorectal tumour biopsies, as compared to normal mucosae. We also found a negative correlation between HLA-E expression and the CD57+ cells infiltrate. Moreover, we analysed HLA-E expression in several colorectal cancer cell lines and demonstrated that IFN-gamma upregulates the expression of membrane HLA-E in vitro. Interestingly, we demonstrated that colorectal cancer cell lines overexpressing HLA-E at the cell surface inhibited NK-mediated cell lysis. Although IFN-gamma regulatory role needs further investigation, we provide evidence suggesting that this cytokine, within the tumour microenvironment, could promote HLA-E translocation to the surface of tumour epithelial cells. Furthermore, we showed that upregulation of HLA-E could be a marker of shorter disease-free survival in Dukes' C patients and we suggest that this molecule renders tumours less susceptible to immune attack.
HLA-E是一种非经典的MHC分子，最近有报道称其在多种人类癌症类型的肿瘤细胞中表达。我们研究了HLA-E在结直肠癌患者中的表达、其临床意义和预后价值，并对其在结直肠癌细胞系中的表达进行了表征。我们通过qRT-PCR在显微切割样本中分析了HLA-E在转录水平的表达，并通过半定量免疫组织化学在42例结直肠癌患者石蜡包埋组织切片上分析了其在蛋白质水平的表达。我们观察到，与正常黏膜相比，在相当比例的结直肠肿瘤活检组织中，HLA-E转录本和蛋白质均自发过度表达。我们还发现HLA-E表达与CD57+细胞浸润之间呈负相关。此外，我们分析了几种结直肠癌细胞系中HLA-E的表达，并证明γ干扰素在体外上调膜HLA-E的表达。有趣的是，我们证明在细胞表面过度表达HLA-E的结直肠癌细胞系抑制NK介导的细胞裂解。尽管γ干扰素的调节作用需要进一步研究，但我们提供的证据表明，在肿瘤微环境中，这种细胞因子可能促进HLA-E转运至肿瘤上皮细胞表面。此外，我们表明HLA-E的上调可能是Dukes' C期患者无病生存期较短的一个标志物，并且我们认为该分子使肿瘤对免疫攻击的敏感性降低。
