Analysis of immunosuppressive states in patients with malignant glioma

恶性胶质瘤患者免疫抑制状态分析

• 批准号: 09671414
• 负责人: NAGANUMA Hirofumi
• 金额: $ 1.98万
• 依托单位: Yamanashi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671414/
• 关键词: malignant glioma; transforming growth factor-beta; thrombospondin; immunosuppression; トロンボスポンジン; 単球

In this study, we investigated to the mechanisms of immunosuppressive states in patients with malignant glioma.1) The effect of IFN-beta on the expression of CD8O and CD86 molecules in peripheral blood monocytes was examined. IFN-beta modulated the expression of those molecules. However, the effect was different between in vitro and in vivo.2) Presense of immunosuppressive IL-12 p40 homodimer was examined in the patients with malignant glioma. Relatively high levels of IL-12 p40 homodimer were present and bioactive p70 heterodimer was not detected in the patients. This suggests that presense of the IL-12 p40 homodimer may inhibit the initiation of immune reaction against glioma cells.3) Production of TSP-1 by malignant glioma cells and role of TSP-1 in the latent TGF-beta activation were examined. All malignant glioma cell lines expressed TSP-1 mRNA and protein, and had the capacity of latent TGF-beta activation. The TGF-beta activation was inhibited by more than 50% by the addition of … More neutralizing anti-TSP-I antibodies. This suggests that TSP-1 predominantly participated in the TGF-beta activation in malignant glioma cells.4) Correlation of TSP-1 expression with malignancy of gliomas was examined. A localization of TSP-i, TGF-beta was examined immunohistochemically in surgically resected glioma tissues. Most glioblastomas highly expressed both TSP-1 and TGF-beta. Anaplastic astrocytomas expressed moderate levels of TSP-i and TGF-beta, On the other hand, the expression of both proteins was weak in low grade gliomas. Normal brain tissues around the tumors were negative or very weakly positive for TSP-i and TGF-beta. The expression of TSP-i and TGF-beta in situ correlated with the histological malignancy of glioma.These data indicate that the presense of the IL-12 p40 homodimer may relates to the immunosuppressive states of the patients and the overexpression of both TSP-i and TGF-beta may increase biological malignancy of malignant gliomas, through generating an active form of TGF-beta which may exert a local immunosuppression in tumor tissues. Biological significance of TSP-1 overexpression, especially its role on tumor cell invasion, in malignant glioma cells is needed to be further investigated. Less

本研究旨在探讨恶性胶质瘤患者免疫抑制状态的机制。1）观察IFN-β对外周血单核细胞CD 80和CD 86分子表达的影响。IFN-β调节这些分子的表达。2）检测恶性胶质瘤患者免疫抑制性IL-12 p40同源二聚体的表达。在患者中存在相对高水平的IL-12 p40同源二聚体，并且未检测到生物活性p70异源二聚体。提示IL-12 p40同源二聚体的存在可能抑制针对胶质瘤细胞的免疫反应的启动。3）检测恶性胶质瘤细胞产生TSP-1以及TSP-1在潜伏性TGF-β活化中的作用。所有恶性胶质瘤细胞系均表达TSP-1 mRNA和蛋白，并具有潜在的TGF-β激活能力。TGF-β活化被添加的抗氧化剂抑制超过50%。 ...更多信息 中和抗TSP-I抗体。这表明TSP-1主要参与恶性胶质瘤细胞中TGF-β的活化。4）检查TSP-1表达与胶质瘤恶性程度的相关性。免疫组织化学法检测手术切除的胶质瘤组织中TSP-1、TGF-β的定位。大多数胶质母细胞瘤高度表达TSP-1和TGF-β。间变性星形细胞瘤表达中等水平的TSP-1和TGF-β，而低级别胶质瘤中这两种蛋白的表达较弱。肿瘤周围的正常脑组织呈阴性或极弱阳性。提示IL-12 p40同源二聚体的存在可能与胶质瘤患者的免疫抑制状态有关，而TGF-β和TSP-1的过度表达可能通过在肿瘤组织中产生活性TGF-β而发挥局部免疫抑制作用，从而增加恶性胶质瘤的生物学恶性度。恶性胶质瘤细胞中TSP-1过表达的生物学意义，特别是其在肿瘤细胞侵袭中的作用有待进一步研究。少