In:
Cancer Science, Wiley, Vol. 109, No. 12 ( 2018-12), p. 3726-3736
Abstract:
Indoleamine 2,3‐dioxygenase 1 ( IDO 1) is a tryptophan‐metabolizing enzyme that is widely distributed in normal or malignant tissues and contributes to immunologic tolerance and immune escape. However, in hepatocellular carcinoma ( HCC ), the characteristics and mechanism of IDO 1 expression have not been well defined. In this study, IDO 1 expression in tumor cells (T‐ IDO 1) was frequently detected (109/112) by immunohistochemistry in formalin‐fixed paraffin‐embedded specimens from HCC patients, and the expression patterns were mostly focal (102/109). Expression of T‐ IDO 1 was significantly associated with the infiltration of CD 8+ T cells ( P = .043), as well as younger age ( 〈 50 years old, P = .02). It was also found that IDO 1 had diffuse expression in inflammatory cells in all specimens, which were defined as antigen‐presenting cells. Significant correlations among IDO 1 , IFNG , and CD 8A transcriptional levels were observed in freshly resected HCC specimens; moreover, no constitutive IDO 1 expression was detected in HCC cell lines until stimulated by interferon‐γ through the JAK 2‐ STAT 1 signaling pathway, but not type I interferon. Survival analyses showed that increased T‐ IDO 1 and CD 8+ T cell infiltration were significantly associated with superior overall survival ( OS ) (T‐ IDO 1, P = .003; CD 8+ T cells, P = .004), and T‐ IDO 1 expression is an independent prognosis factor in both OS and disease‐free survival ( OS , P = .007; disease‐free survival, P = .044). These findings indicated that T‐ IDO 1 expression in HCC is common and is dominantly driven by the host antitumor immune response, which is a favorable prognostic factor in HCC .
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-12
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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