Yoshitake Yoshihiro, Nakatsura Tetsuya, Monji Mikio, Senju Satoru, Matsuyoshi Hidetake, Tsukamoto Hirotake, Hosaka Seiji, Komori Hiroyuki, Fukuma Daiki, Ikuta Yoshiaki, Katagiri Toyomasa, Furukawa Yoichi, Ito Hiromi, Shinohara Masanori, Nakamura Yusuke, Nishimura Yasuharu
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Clin Cancer Res. 2004 Oct 1;10(19):6437-48. doi: 10.1158/1078-0432.CCR-04-0841.
To establish effective antitumor immunotherapy for esophageal cancer, we tried to identify an useful target antigen of esophageal cancer.
We did cDNA microarray analysis to find a novel candidate antigen, proliferation potential-related protein (PP-RP). We examined cytotoxicity against tumor cells in vitro and in vivo of CTLs specific to PP-RP established from esophageal cancer patients.
In 26 esophageal cancer tissues, an average of relative ratio of the expression of the PP-RP mRNA in cancer cells versus adjacent normal esophageal tissues was 396.2. Immunohistochemical analysis revealed that, in 20 of the 22 esophageal cancer tissues, PP-RP protein was strongly expressed only in the cancer cells and not so in normal esophageal epithelial cells. PP-RP protein contains 10 epitopes recognized by HLA-A24-restricted CTLs. These CTLs, generated from HLA-A24-positive esophageal cancer patients, had cytotoxic activity against cancer cell lines positive for both PP-RP and HLA-A24. Furthermore, adoptive transfer of the PP-RP-specific CTL line inhibited the growth of a human esophageal cancer cell line engrafted in nude mice.
The expression of PP-RP in esophageal cancer cells was significantly higher than in normal cells, and the CTLs recognizing PP-RP killed tumor cells in vitro and also showed tumor rejection effects in a xenograft model. Therefore, PP-RP may prove to be an ideal tumor antigen useful for diagnosis and immunotherapy for patients with esophageal cancer. cDNA microarray analysis is a useful method to identify ideal tumor-associated antigens.
为建立有效的食管癌抗肿瘤免疫疗法，我们试图鉴定一种有用的食管癌靶抗原。
我们进行了cDNA微阵列分析以寻找一种新的候选抗原，即增殖潜能相关蛋白（PP-RP）。我们检测了从食管癌患者中建立的针对PP-RP的细胞毒性T淋巴细胞（CTL）在体外和体内对肿瘤细胞的细胞毒性。
在26例食管癌组织中，癌细胞中PP-RP mRNA表达的相对平均比值与相邻正常食管组织相比为396.2。免疫组织化学分析显示，在22例食管癌组织中的20例中，PP-RP蛋白仅在癌细胞中强烈表达，而在正常食管上皮细胞中则不明显。PP-RP蛋白包含10个可被HLA-A24限制性CTL识别的表位。这些从HLA-A24阳性食管癌患者中产生的CTL对PP-RP和HLA-A24均呈阳性的癌细胞系具有细胞毒性活性。此外，PP-RP特异性CTL系的过继转移抑制了接种于裸鼠的人食管癌细胞系的生长。
PP-RP在食管癌细胞中的表达明显高于正常细胞，识别PP-RP的CTL在体外可杀伤肿瘤细胞，并且在异种移植模型中也显示出肿瘤排斥作用。因此，PP-RP可能被证明是一种对食管癌患者诊断和免疫治疗有用的理想肿瘤抗原。cDNA微阵列分析是鉴定理想肿瘤相关抗原的一种有用方法。
