Ishio Tetsuya, Goto Shigeru, Tahara Kouichirou, Tone Shigenobu, Kawano Katsunori, Kitano Seigo
Department of Surgery I, Oita Medical University, Hasama-machi, Oita, Japan.
J Gastroenterol Hepatol. 2004 Mar;19(3):319-26. doi: 10.1111/j.1440-1746.2003.03259.x.
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme. Recent studies have focused on the immunoregulatory role of IDO in mononuclear cells. The role of IDO in hepatocellular carcinoma (HCC) cell lines and HCC patients was examined.
The expression of IDO mRNA in peripheral blood mononuclear cells (PBMC) cocultured with HCC cell lines was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The cytotoxicity of PBMC against HCC cell lines cultured with and without IDO inhibitor was examined by sodium 51chromate release assay. In the tumor portion of 21 HCC patients, the expression of mRNA of IDO, tryptophan 2,3-dioxygenase and some cytokines was detected by RT-PCR. The expression and distribution of IDO protein in HCC specimens was analyzed by immunohistochemistry.
The IDO mRNA was strongly induced in PBMC cocultured with HepG2 and PLC/PRF/5 and faintly induced in PBMC cocultured with Hep3B and HuH7. The cytotoxicity of PBMC against HCC cell lines was directly proportional to the level of expression of IDO mRNA and reduced by IDO inhibitor. The expression of IDO mRNA in the tumor portion was detected in 12 out of 21 HCC patients. Immunohistochemistry revealed that the IDO-positive cells were identified to be tumor-infiltrating cells, not tumor cells. The IDO mRNA correlated significantly with gene expression of interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta. The recurrence-free survival rate of IDO-positive HCC patients was significantly higher than that of IDO-negative HCC patients (P<0.05).
These results suggest that IDO is a necessary enzyme for anticancer immune reactions of tumor-infiltrating cells.
吲哚胺2,3-双加氧酶（IDO）是一种色氨酸分解代谢酶。最近的研究聚焦于IDO在单核细胞中的免疫调节作用。本研究检测了IDO在肝癌（HCC）细胞系和HCC患者中的作用。
采用逆转录-聚合酶链反应（RT-PCR）检测与HCC细胞系共培养的外周血单核细胞（PBMC）中IDO mRNA的表达。采用51铬酸钠释放试验检测有无IDO抑制剂培养时PBMC对HCC细胞系的细胞毒性。采用RT-PCR检测21例HCC患者肿瘤组织中IDO、色氨酸2,3-双加氧酶及一些细胞因子的mRNA表达。采用免疫组织化学分析IDO蛋白在HCC标本中的表达及分布。
与HepG2和PLC/PRF/5共培养的PBMC中IDO mRNA被强烈诱导，与Hep3B和HuH7共培养的PBMC中IDO mRNA被微弱诱导。PBMC对HCC细胞系的细胞毒性与IDO mRNA表达水平成正比，并被IDO抑制剂降低。21例HCC患者中有12例在肿瘤组织中检测到IDO mRNA表达。免疫组织化学显示IDO阳性细胞为肿瘤浸润细胞，而非肿瘤细胞。IDO mRNA与干扰素-γ、肿瘤坏死因子-α和白细胞介素-1β的基因表达显著相关。IDO阳性HCC患者的无复发生存率显著高于IDO阴性HCC患者（P<0.05）。
这些结果表明IDO是肿瘤浸润细胞抗癌免疫反应所必需的酶。
