Mechanisms underlying inhibition of tumor-immunology in malignant glioma and development of immune-activation therapy using suicide-chimeric molecule

恶性胶质瘤是人类肿瘤中恶性程度最高的肿瘤。尽管广泛的临床试验，一个良好的临床结果仍然是一个难以捉摸的目标。由于浸润程度高，对照射和抗癌药物有抵抗力，以及血脑屏障的存在抑制药物进入中枢神经系统等因素阻碍了治疗的成功。此外，肿瘤细胞产生的免疫抑制分子抑制TGF-β等抗肿瘤免疫的建立。在本项目中，我们利用组织芯片初步研究了TGF-β表达与恶性胶质瘤患者预后的关系。但是，我们没有显示它们之间的统计显著性。为了寻找恶性胶质瘤产生的新型免疫抑制剂，我们研究了恶性但预后良好的间变性少突胶质细胞瘤特异性表达的分子。在这些分子中，我们专注于ABCA2，一种膜蛋白。实时荧光定量PCR、免疫印迹和免疫组织化学研究表明，ABCA2在少突胶质细胞肿瘤中的表达高于星形胶质细胞肿瘤。虽然ABCA2在肿瘤免疫学中的生物学作用仍在研究中，但有趣的是，ABCA2可以作为少突胶质细胞瘤的一种新的肿瘤标志物。

Malignant glioma is the most malignant tumor of the human neoplasms. Despite extensive clinical trials, a good clinical outcome has remained an elusive goal. The success of treatment is hampered by factors such as high degree of infiltration, resistance against irradiation and anti-cancer drugs, and existence of the blood brain barriers that inhibit the drug delivery into the central nervous system. In addition, it has been postulated that immuno-suppressive molecules produced by the tumor cells inhibit the establishment of the anti-tumor immunity such as TGF-β.In this project, we initially investigated the correlation between the expression of TGF-β and prognosis of the patients with malignant glioma using tissue microarray. However, we failed to show the statistical significance between them. To search for the novel immuno-suppressant produced by the malignant glioma, we investigated the molecules that were specifically expressed by the anaplastic oligodendroglioma, which is malignant but has good prognosis.Among these molecules, we focused on ABCA2, a membranous protein. Quantitative real-time PCR, immunoblot and immunohistochemical study demonstrated that ABCA2 is highly expressed in oligodendroglial tumors than in astrocytic tumors. Although biological role on the tumor immunology is still under investigation, it is interesting that ABCA2 could serve as a novel tumor marker for oligodendrogliomas.