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

Byeong-Joo Noh; Gun Moo Choi; Hyuk Jai Jang; Chung Hyeun Ma; Ho-Suk Oh; Moonho Kim; Dae-Woon Eom

doi:10.3892/ol.2022.13493

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

Oncol Lett. 2022 Sep 5;24(4):373. doi: 10.3892/ol.2022.13493. eCollection 2022 Oct.

Authors

Byeong-Joo Noh¹, Gun Moo Choi², Hyuk Jai Jang², Chung Hyeun Ma², Ho-Suk Oh³, Moonho Kim³, Dae-Woon Eom¹

Affiliations

¹ Department of Pathology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do 25440, Republic of Korea.
² Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do 25440, Republic of Korea.
³ Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do 25440, Republic of Korea.

Abstract

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^high/CD8^low subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with IDO1^high/CD8^high, IDO1^low/CD8^high and IDO1^low/CD8^low 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.

Keywords: 3-dioxygenase 1; bile duct cancer; indoleamine 2; tumor infiltrating lymphocytes.

Grants and funding

Professor Dae-Woon Eom received a research grant (grant no. NRF-2020R1F1A1067158) of the Basic Science Research Program from the National Research Foundation of Korea funded by the Ministry of Science and ICT, and a grant (grant no. 2020-IB008) from the Gangneung Asan Hospital Biomedical Research Center Promotion Fund.