The Prognostic Implications of Immune Classification Using IDO1 Expression in Extrahepatic Bile Duct Carcinoma

Background: Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine (Kyn) and induces immune tolerance in tumour cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. Methods: An immunohistochemical microarray analysis of IDO1 expression was performed for 77 surgically resected cases of EHBDC, and the results were compared with various clinicopathologic variables including survival data. CD8+ tumour infiltrating lymphocytes (TILs) were also investigated to elucidate their relationship with IDO1 expression and prognosis through a combination analysis with IDO1 expression. Results: 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 IDO1high /CD8low subgroup showed the worst prognosis in terms of overall survival (P = 0.025, Cox risk ratio = 2.168) and disease-free survival (P = 0.015, Cox risk ratio = 2.460) in a multivariate analysis. Conclusions: Our study confirmed that high IDO1 expression was correlated 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 prediction tool in the patients with EHBDC.