Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer
Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer
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DOI：
10.1159/000334089
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发表时间：
2012-01-01
期刊：
影响因子：
5
通讯作者：
Lucia Combita, Alba
中科院分区：
文献类型：
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作者：
Antonia Rodriguez, Josefa;Galeano, Liliana;Lucia Combita, Alba
虽然高危型人乳头瘤病毒（HPV）是宫颈癌发病机制中的一个重要危险因素，但越来越多的证据表明，避免免疫监视的能力似乎与HPV的转化潜力和快速进展为癌症有关。在其他癌症模型中，IL-10通过下调人类白细胞抗原I类（HLA-I）表达或通过增加HLA-G表达来损害抗肿瘤免疫应答。为了了解这些改变如何有助于逃避宫颈癌的免疫监视，我们分析了HLA-I，HLA-G和IL-10的表达，通过免疫组织化学在63例宫颈上皮内瘤样病变III（CIN-III）和宫颈癌患者的活检。免疫组化显示50/59例HLA-I表达缺失或弱表达。在这些病例中，杂合性丢失的比例很高。IL-10和HLA-G表达分别在46.6%和27.6%的病例中观察到。在87.5%的HLA-G阳性病例中发现了IL-10的同时上调（p = 0.000）。类似地，发现IL-10表达与HLA-I下调之间存在显著关联（p = 0.028）。最后，我们观察到HLA-G在HLA-I下调患者中的表达高于HLA-I表达正常的患者（p = 0.004）。我们的研究结果表明，在宫颈癌中，IL-10的表达可能通过上调HLA-G表达和下调HLA I类表达诱导免疫抑制环境。版权所有（C）2011 S. Karger AG，巴塞尔
Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression. Copyright (C) 2011 S. Karger AG, Basel