Shichijo Shigeki, Azuma Kohichi, Komatsu Nobukazu, Kawamoto Naoki, Takedatsu Hiroko, Shomura Hiroki, Sawamizu Hiromi, Maeda Yoshiaki, Ito Masaaki, Itoh Kyogo
Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Int J Mol Med. 2003 Dec;12(6):895-902.
The objective of this study was to identify novel genes and peptides capable of inducing tumor-reactive cytotoxic T lymphocytes (CTLs) in cancer patients with an HLA-B46 allele, which is preferentially expressed in Asians. We show that two genes encoding splicing factor (SF) 2 and inosine triphosphate pyrophosphatase (ITPA) have epitopes recognized by HLA-B46-restricted and tumor cell-reactive CTL lines established from tumor-infiltrating lymphocytes of colon cancer. The SF2 is essential for constitutive pre-mRNA splicing, while the enzyme ITPA controls nucleotide levels. The mRNA expression levels of these genes were higher in tumor cells than those in normal tissues. Five peptides, three from SF2 and two from ITPA, had the ability to induce HLA-B46-restricted and peptide-specific CTLs reactive to tumor cells in peripheral blood mononuclear cells of cancer patients. These results may provide new information for better understanding of host-tumor interaction at the molecular level and the development of peptide-based immunotherapy for HLA-B46+ cancer patients.
本研究的目的是在携带HLA - B46等位基因（该基因在亚洲人中优先表达）的癌症患者中鉴定能够诱导肿瘤反应性细胞毒性T淋巴细胞（CTL）的新基因和肽。我们发现，两个分别编码剪接因子（SF）2和肌苷三磷酸焦磷酸酶（ITPA）的基因具有表位，这些表位可被从结肠癌肿瘤浸润淋巴细胞建立的HLA - B46限制性和肿瘤细胞反应性CTL系识别。SF2对组成型前体mRNA剪接至关重要，而ITPA酶则控制核苷酸水平。这些基因的mRNA表达水平在肿瘤细胞中高于正常组织。来自SF2的三个肽和来自ITPA的两个肽能够在癌症患者外周血单核细胞中诱导对肿瘤细胞有反应的HLA - B46限制性和肽特异性CTL。这些结果可能为在分子水平上更好地理解宿主与肿瘤的相互作用以及为HLA - B46 +癌症患者开发基于肽的免疫疗法提供新信息。
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