Division of Maxillofacial Surgery, Innsbruck Medical University, Austria.
Oral Oncol. 2011 May;47(5):352-7. doi: 10.1016/j.oraloncology.2011.03.007. Epub 2011 Mar 25.
Indoleamine 2,3 dioxygenase (IDO) is a negative immune regulator and was found to be a prognostic marker in several tumor entities. In this study, we analysed IDO expression in oral squamous cell carcinoma (OSCC) regarding patient's prognosis. Additionally, expression of IDO like-1 gene (INDOL-1) was analysed. Tumor tissue from 88 patients with OSCC was analysed by immunohistochemistry for IDO expression. The influence of IDO expression on survival was studied by multivariate Cox regression, adjusting for established clinical prognostic parameters. Real time PCR of tumor samples was performed in a subgroup of patients to analyse mRNA expression of IDO and INDOL-1. IDO high-expression was observed in 44.2% of OSCC patients. No significant correlation was found between IDO expression and clinical stage, sex, age, tumor site, tumor size, metastasis or tumor grade. The median overall survival time was 3.1 years for patients with IDO low tumors, compared to 1.36 years for IDO high tumors (P=.028). Subset analysis of patients receiving adjuvant radio-chemotherapy showed a significant difference (P=.0046) in overall survival between IDO low tumors (3.35 years) and IDO high tumors (1.26 years). In contrast, the impact of IDO expression on survival time in patients without adjuvant therapy was not significant (P=.574). Interestingly, INDOL-1 was not expressed in OSCC. IDO high expression represents a significant negative prognostic factor in patients with OSCC, especially in those patients undergoing adjuvant radiochemotherapy. Our data support the suggestion, co-administration of small-molecule IDO inhibitors could represent a promising new strategy to increase the anti-tumor activity of radio-chemotherapy in patients with IDO positive OSCC.
吲哚胺 2,3-双加氧酶（IDO）是一种负性免疫调节剂，已被发现是多种肿瘤实体的预后标志物。在这项研究中，我们分析了口腔鳞状细胞癌（OSCC）中 IDO 的表达与患者预后的关系。此外，还分析了 IDO 样-1 基因（INDOL-1）的表达。通过免疫组织化学分析 88 例 OSCC 患者的肿瘤组织中 IDO 的表达。通过多变量 Cox 回归分析，调整了既定的临床预后参数，研究了 IDO 表达对生存的影响。在患者亚组中进行了肿瘤样本的实时 PCR，以分析 IDO 和 INDOL-1 的 mRNA 表达。在 44.2%的 OSCC 患者中观察到 IDO 高表达。IDO 表达与临床分期、性别、年龄、肿瘤部位、肿瘤大小、转移或肿瘤分级之间未发现显著相关性。IDO 低肿瘤患者的中位总生存期为 3.1 年，而 IDO 高肿瘤患者为 1.36 年（P=.028）。接受辅助放化疗的患者亚组分析显示，IDO 低肿瘤（3.35 年）和 IDO 高肿瘤（1.26 年）之间的总生存时间有显著差异（P=.0046）。相比之下，辅助治疗患者的 IDO 表达对生存时间的影响无统计学意义（P=.574）。有趣的是，OSCC 中未表达 INDOL-1。IDO 高表达是 OSCC 患者的一个显著的负预后因素，尤其是在接受辅助放化疗的患者中。我们的数据支持这样的建议，即联合使用小分子 IDO 抑制剂可能是一种很有前途的新策略，可以提高 IDO 阳性 OSCC 患者放化疗的抗肿瘤活性。
