Expression and prognostic impact of indoleamine 2,3-dioxygenase in oral squamous cell carcinomas

Abstract

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.