Schmitz M, Temme A, Senner V, Ebner R, Schwind S, Stevanovic S, Wehner R, Schackert G, Schackert H K, Fussel M, Bachmann M, Rieber E P, Weigle B
Medical Faculty, Institute of Immunology, Technical University of Dresden, Dresden, Germany.
Br J Cancer. 2007 Apr 23;96(8):1293-301. doi: 10.1038/sj.bjc.6603696. Epub 2007 Mar 20.
Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A(*)0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma.
恶性胶质瘤患者的预后并未得到显著改善。作为一种新型治疗理念的特异性免疫疗法关键取决于靶抗原，大多数胶质瘤中这些靶抗原高度过表达，但此类抗原的数量仍然非常有限。通过筛选一个表达数据库以寻找在恶性胶质瘤中过表达但在正常组织中表达极低的转录本，从而鉴定出了SOX2。通过实时PCR进一步研究了肿瘤组织和正常组织中SOX2 mRNA的表达。与来自汇集的正常脑组织的cDNA相比，SOX2在几乎所有（10个中的9个）恶性胶质瘤样本中均过表达，而在其他非恶性组织中的表达几乎可以忽略不计。通过蛋白质免疫印迹法和免疫荧光法验证了胶质瘤细胞系和肿瘤组织中SOX2蛋白的表达。免疫组织化学显示，在所研究的所有恶性胶质瘤组织中均有SOX2蛋白表达，染色的肿瘤细胞比例为6%至66%。测试了人白细胞抗原-A(*)0201限制性的SOX2衍生肽对胶质瘤反应性CD8+细胞毒性T淋巴细胞（CTL）的激活作用。产生了针对肽TLMKKDKYTL的特异性CTL，其能够裂解胶质瘤细胞。SOX2的丰富且胶质瘤限制性过表达以及SOX2特异性和肿瘤反应性CTL的产生可能使该抗原成为基于T细胞的胶质瘤免疫治疗的靶点。
