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子宫内膜癌中免疫调节分子 HLA-G、HLA-E 和 IDO 的表达分析。

Expression analysis of immune-regulatory molecules HLA-G, HLA-E and IDO in endometrial cancer.

机构信息

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia.

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia; Department of Anatomopathology, Salah Azaiz Institute, Tunis, Tunisia.

出版信息

Hum Immunol. 2020 Jun;81(6):305-313. doi: 10.1016/j.humimm.2020.03.008. Epub 2020 Apr 6.

DOI:10.1016/j.humimm.2020.03.008
PMID:32273131
Abstract

HLA-G has been widely implicated in advanced cancers through different pathways of immunosuppression allowing tumor escape. Contrarily, HLA-E has a controversial role in the tumor escape from the immune system. IDO catabolic enzyme is known to be up-regulated in many tumors types allowing their immune escape. Based on these considerations, we investigated the expression of HLA-G, HLA-E and IDO molecules in endometrial cancer (EC) and their association with prognostic clinicopathologic parameters. Their expression were checked in tumoral and adjacent endometrial tissues. Both HLA-G and IDO immunostaining were significantly increased in EC tissues compared to normal residual endometrial glands (Mann Whitney U-test, p = 0.0001 and p = 0,020 respectively). However, HLA-E was highly expressed in tumoral tissues as well as in normal residual endometrial glands (respectively, 100% and 81.8%). Increased HLA-G expression levels were observed in high histological grade (grade 3), and in the non-endometrioid type 2 EC. Unexpectedly, patients with IDO Low expression had significantly impaired overall survival compared to patients with IDO High (log-rank p = 0.021). Conversely, HLA-E low expression was associated to an improved overall survival EC (log-rank p = 0.004). We concluded that, HLA-G and IDO are highly expressed in EC compared to adjacent normal endometrial tissues, that might be interesting for the EC outcome.

摘要

HLA-G 通过不同的免疫抑制途径广泛参与晚期癌症,从而使肿瘤逃脱免疫监视。相反,HLA-E 在肿瘤逃避免疫系统方面的作用存在争议。吲哚胺 2,3-双加氧酶(IDO)分解代谢酶在许多肿瘤类型中被上调,从而允许肿瘤免疫逃逸。基于这些考虑,我们研究了 HLA-G、HLA-E 和 IDO 分子在子宫内膜癌(EC)中的表达及其与预后临床病理参数的关系。在肿瘤和邻近的子宫内膜组织中检查了它们的表达。与正常残留子宫内膜腺体相比,HLA-G 和 IDO 的免疫染色在 EC 组织中均显著增加(Mann-Whitney U 检验,p=0.0001 和 p=0.020)。然而,HLA-E 在肿瘤组织和正常残留子宫内膜腺体中均高度表达(分别为 100%和 81.8%)。在高组织学分级(3 级)和非子宫内膜样 2 型 EC 中观察到 HLA-G 表达水平增加。出乎意料的是,与 IDO 高表达患者相比,IDO 低表达患者的总生存率明显降低(对数秩检验,p=0.021)。相反,HLA-E 低表达与 EC 患者的总生存率提高相关(对数秩检验,p=0.004)。我们得出结论,与邻近的正常子宫内膜组织相比,HLA-G 和 IDO 在 EC 中高表达,这可能对 EC 的预后有意义。

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