Prognostic implications of immune classification using IDO1 expression in extrahepatic bile duct carcinoma.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine and induces immune tolerance in tumor cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. Therefore, the present study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. An immunohistochemical microarray analysis of IDO1 expression was performed for 76 surgically resected cases of EHBDC. CD8 tumor infiltrating lymphocytes (TILs) were also investigated through a combination analysis with IDO1 expression. IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8 TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001) and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8 TIL state, the IDO1/CD8 subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with IDO1/CD8, IDO1/CD8 and IDO1/CD8 subgroups. High IDO1 expression was associated with a decreased number of CD8 TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8 TIL subgrouping can be a useful prognostic and predictive tool in patients with EHBDC.