Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France.
Am J Pathol. 2013 Feb;182(2):540-52. doi: 10.1016/j.ajpath.2012.10.021. Epub 2012 Dec 4.
Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex (MHC) class I molecule involved in immune tolerance processes, playing an important role in the maintenance of the semi-allogeneic fetus. Although HLA-G expression is restricted in normal tissues, it is broadly expressed in malignant tumors and may favor tumor immune escape. We analyzed HLA-G protein and mRNA expression in tumor samples from patients with glioblastoma collected in France, Denmark, and Brazil. We found HLA-G protein expression in 65 of 108 samples and mRNA in 20 of 21 samples. The absence of HLA-G protein expression was associated with a better long-term survival rate. The mechanisms underlying HLA-G gene expression were investigated in glioma cell lines U251MG, D247MG, and U138MG. Induction of HLA-G transcriptional activity was dependent of 5-aza-2'-deoxycytidine treatment and enhanced by interferon-γ. HLA-G protein expression was observed in U251MG cells only. These cells exhibited a permissive chromatin state at the HLA-G gene promoter and the highest levels of induced HLA-G transcriptional activity following 5-aza-2'-deoxycytidine treatment. Several antigen-presenting machinery components were up-regulated in U251MG cells after demethylating and IFN-γ treatments, suggesting an effect on the up-regulation of HLA-G cell surface expression. Therefore, because of its role in tumor tolerance, HLA-G found to be expressed in glioblastoma samples should be taken into consideration in clinical studies on the pathology and in the design of therapeutic strategies to prevent its expression in HLA-G-negative tumors.
人类白细胞抗原-G（HLA-G）是一种非经典的主要组织相容性复合体（MHC）I 类分子，参与免疫耐受过程，在维持半同种异体胎儿中发挥重要作用。尽管 HLA-G 的表达在正常组织中受到限制，但它在恶性肿瘤中广泛表达，可能有利于肿瘤免疫逃逸。我们分析了法国、丹麦和巴西收集的胶质母细胞瘤患者肿瘤样本中的 HLA-G 蛋白和 mRNA 表达。我们发现 108 个样本中有 65 个表达 HLA-G 蛋白，21 个样本中有 20 个表达 HLA-G mRNA。HLA-G 蛋白表达缺失与长期生存率的提高相关。在 U251MG、D247MG 和 U138MG 胶质母细胞瘤细胞系中研究了 HLA-G 基因表达的机制。HLA-G 转录活性的诱导依赖于 5-氮杂-2'-脱氧胞苷处理，并被干扰素-γ增强。仅在 U251MG 细胞中观察到 HLA-G 蛋白表达。这些细胞在 HLA-G 基因启动子处表现出允许的染色质状态，并且在 5-氮杂-2'-脱氧胞苷处理后具有最高水平的诱导 HLA-G 转录活性。在去甲基化和 IFN-γ 处理后，U251MG 细胞中几种抗原呈递机制成分上调，提示其对 HLA-G 细胞表面表达上调的影响。因此，由于其在肿瘤耐受中的作用，在关于病理的临床研究和设计预防 HLA-G-阴性肿瘤中表达的治疗策略时，应考虑在胶质母细胞瘤样本中发现 HLA-G 表达。
