Analysis of immunosuppressive states in patients with malignant glioma

本研究探讨了恶性胶质瘤患者免疫抑制状态的机制。1)检测ifn - β对外周血单核细胞cd80和CD86分子表达的影响。ifn调节了这些分子的表达。然而，体外和体内的效果是不同的。2)在恶性胶质瘤患者中检测免疫抑制IL-12 p40同型二聚体的存在。患者中存在较高水平的IL-12 p40同型二聚体，未检测到生物活性p70异源二聚体。这表明il - 12p40同型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及TSP-1在tgf - β潜伏活化中的作用。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的激活被添加…更多的中和性抗tsp - 1抗体抑制了50%以上。这表明TSP-1主要参与了恶性胶质瘤细胞中tgf - β的激活。4)检测TSP-1表达与胶质瘤恶性程度的相关性。在手术切除的胶质瘤组织中，用免疫组织化学方法检测了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，另一方面，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tsp - 1和tgf - β呈阴性或极弱阳性。tgf - β和tsp - 1的原位表达与胶质瘤的组织学恶性程度相关。这些数据表明，il - 12p40同型二聚体的存在可能与患者的免疫抑制状态有关，tsp -1和tgf - β的过表达可能通过产生活性形式的tgf - β在肿瘤组织中发挥局部免疫抑制作用，从而增加恶性胶质瘤的生物恶性程度。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

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