Introduction: Indoleamine 2,3-dioxygenase (IDO) is activated by IFN-γ and via local tryptophan depletion modulates T-cell function and promotes immune tolerance. IDO has been demonstrated to be critically involved in maternal tolerance and recent attention has turned towards its role in immune evasion of certain tumors. However, whether IDO expression is involved in tumor growth control or chemoresistance still remains controversial. Patients and Methods: Semiquantitative immunohistochemistry was used to evaluate and score IDO-expression in tissue samples of 88 patients with oral squamous cell cancer and was then correlated with various clinical parameters.

Results: Immunohistochemical scores revealed IDO-high expression in 39/88 (44.3%) tumor specimens, whereas 49/88 (55.7%) cases showed low IDO expression levels. IDO-high immunoreactivity significantly correlated with the frequency of metastases (P=0.003). Survival analysis according to Kaplan Meier revealed a significant correlation for patients with IDO-high or -low expressing primary tumors. Most striking, highest significant correlations were found in those patients receiving adjuvant chemotherapy. Furthermore, by multivariate Coxs analysis IDO-high expression emerged as independent prognostic variable.

Conclusion: These are the first clinical data to show that IDO might be involved in mechanisms leading to chemoresistance in patients with oral cancer. IDO-high expression by oral squamous cancer cells significantly contributes to overall survival especially when exposed to adjuvant therapy.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA