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 inv...

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Published in:Oncology letters 2022-10, Vol.24 (4), p.1, Article 373
Main Authors: Noh, Byeong-Joo, Choi, Gun Moo, Jang, Hyuk Jai, Ma, Chung Hyeun, Oh, Ho-Suk, Kim, Moonho, Eom, Dae-Woon
Format: Article
Language:English
Subjects:
Analysis
Bile ducts
Cancer
Carcinoma
Cholangiocarcinoma
Development and progression
DNA microarrays
Enzymes
Immunotherapy
Medical prognosis
Metastasis
Pancreaticoduodenectomy
Patients
Polymers
Software
Tumors
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Summary: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.sup.+] 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.sup.+] 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.sup.+] TIL state, the [IDO1.sup.high]/[CD8.sup.low] subgroup was decreased in terms of overall survival (P=0.025) and disease-free survival (P=0.015) compared with [IDO1.sup.high]/[CD8.sup.high], [IDO1.sup.low]/[CD8.sup.high] and [IDO1.sup.low]/[CD8.sup.low] subgroups. High IDO1 expression was associated with a decreased number of [CD8.sup.+] TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/[CD8.sup.+] TIL subgrouping can be a useful prognostic and predictive tool in patients with EHBDC. Key words: indoleamine 2, 3-dioxygenase 1, bile duct cancer, tumor infiltrating lymphocytes
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2022.13493