Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas
Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas
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DOI：
10.1111/j.1349-7006.2005.00073.x
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发表时间：
2005-08-01
期刊：
影响因子：
5.7
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
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作者：
Watanabe, T;Suda, T;Nakamura, Y
我们先前对20例胃粘膜型胃癌进行了基因表达谱分析，并确定了一组基因，与相应的非癌组织相比，这些基因在癌组织中的表达水平升高。在本研究中，我们专注于免疫球蛋白超家族11基因（IGSF 11）。在大肠癌、肝细胞癌和胃肠道型胃癌中表达也升高。北方杂交分析表明，该基因在精巢和卵巢中表达丰富。这些数据表明，IGSF 11是一个很好的候选肿瘤-睾丸抗原。此外，通过siRNA抑制IGSF 11抑制胃癌细胞的生长。为了探讨IGSF 11肽疫苗临床应用的可能性，我们合成了IGSF 11的候选表位肽，并测试了这些肽是否能诱导IGSF 11特异性CTL。因此，我们成功地建立了寡克隆CTL刺激IGSF 11 -9-207（ALSSGLYQC）。此外，我们还使用IGSF 11 -9-207的锚修饰肽IGSF 11 -9V（ALSSGLYQV）建立了另外的CTL。这些肽以HLA-A*0201限制的方式显示IGSF 11特异性细胞毒活性，表明这些肽可用于癌症免疫治疗。这些发现为胃、结肠和肝脏的癌变提供了新的见解，并将有助于开发针对多种人类癌症的新治疗策略。
We previously performed gene expression profile analyses of 20 intestinal-type gastric cancers, and identified a set of genes whose expression levels were elevated in cancer tissues compared to their corresponding non-cancerous tissues. In the present study we focused on the immunoglobulin superfamily 11 gene (IGSF11). Its expression was also elevated in colorectal cancers and hepatocellular carcinomas as well as intestinal-type gastric cancers. Northern blot analysis showed that it was expressed abundantly in testis and ovary. These data suggest that IGSF11 is a good candidate of cancer-testis antigen. Furthermore, suppression of IGSF11 by siRNA retarded the growth of gastric cancer cells. To investigate the possibility of clinical application of peptide vaccine to IGSF11, we synthesized candidate epitope peptides for IGSF11 and tested whether the peptides elicit IGSF11-specific CTL. As a result, we successfully established oligo-clonal CTL by stimulation with IGSF11-9-207 (ALSSGLYQC). In addition, we also established additional CTL using IGSF11-9V (ALSSGLYQV), anchor-modified peptides of IGSF11-9-207. These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy. These findings have provided a novel insight into carcinogenesis of the stomach, colon and liver, and will be helpful for the development of novel therapeutic strategies to a wide range of human cancers.