Mechanism and prognostic value of indoleamine 2,3-dioxygenase 1 expressed in hepatocellular carcinoma.
Mechanism and prognostic value of indoleamine 2,3-dioxygenase 1 expressed in hepatocellular carcinoma.
复制标题
DOI：
10.1111/cas.13811
复制
发表时间：
2018-12
期刊：
影响因子：
5.7
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Li S;Han X;Lyu N;Xie Q;Deng H;Mu L;Pan T;Huang X;Wang X;Shi Y;Zhao M
吲哚胺 2,3-双加氧酶 1 (IDO1) 是一种色氨酸代谢酶，广泛分布于正常或恶性组织中，有助于免疫耐受和免疫逃逸。然而，在肝细胞癌（HCC）中，IDO1表达的特征和机制尚未明确。在本研究中，免疫组织化学法在 HCC 患者的福尔马林固定石蜡包埋标本中经常检测到肿瘤细胞 (T-IDO1) 中的 IDO1 表达 (109/112)，并且表达模式大多为局灶性 (102/109)。 T-IDO1 的表达与 CD8+ T 细胞的浸润 (P = .043) 以及年轻年龄 (<50 岁，P = .02) 显着相关。还发现IDO1在所有标本的炎症细胞中广泛表达，这些炎症细胞被定义为抗原呈递细胞。在新鲜切除的 HCC 标本中观察到 IDO1、IFNG 和 CD8A 转录水平之间存在显着相关性；此外，在通过 JAK2-STAT1 信号通路受到干扰素-γ 刺激之前，HCC 细胞系中未检测到 IDO1 组成型表达，但 I 型干扰素未检测到。生存分析表明，T-IDO1 和 CD8+ T 细胞浸润增加与较高的总生存期 (OS) 显着相关（T-IDO1，P = .003；CD8+ T 细胞，P = .004），并且 T-IDO1 表达是 OS 和无病生存期的独立预后因素（OS，P = .007；无病生存期，P = .044）。这些发现表明，HCC 中 T-IDO1 表达很常见，并且主要由宿主抗肿瘤免疫反应驱动，这是 HCC 中有利的预后因素。
Indoleamine 2,3‐dioxygenase 1 (IDO1) 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 IDO1 expression have not been well defined. In this study, IDO1 expression in tumor cells (T‐IDO1) 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‐IDO1 was significantly associated with the infiltration of CD8+ T cells (P = .043), as well as younger age (<50 years old, P = .02). It was also found that IDO1 had diffuse expression in inflammatory cells in all specimens, which were defined as antigen‐presenting cells. Significant correlations among IDO1,IFNG, and CD8A transcriptional levels were observed in freshly resected HCC specimens; moreover, no constitutive IDO1 expression was detected in HCC cell lines until stimulated by interferon‐γ through the JAK2‐STAT1 signaling pathway, but not type I interferon. Survival analyses showed that increased T‐IDO1 and CD8+ T cell infiltration were significantly associated with superior overall survival (OS) (T‐IDO1, P = .003; CD8+ T cells, P = .004), and T‐IDO1 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‐IDO1 expression in HCC is common and is dominantly driven by the host antitumor immune response, which is a favorable prognostic factor in HCC.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
25.7
作者：
Bertuccio, Paola;Turati, Federica;Negri, Eva
通讯作者：
Negri, Eva
DOI：
10.1007/s00262-018-2190-4
发表时间：
2018-08
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Brown ZJ;Yu SJ;Heinrich B;Ma C;Fu Q;Sandhu M;Agdashian D;Zhang Q;Korangy F;Greten TF
通讯作者：
Greten TF
DOI：
10.1084/jem.189.9.1363
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Munn DH;Shafizadeh E;Attwood JT;Bondarev I;Pashine A;Mellor AL
通讯作者：
Mellor AL
影响因子：
7.3
作者：
Heeren AM;van Dijk I;Berry DRAI;Khelil M;Ferns D;Kole J;Musters RJP;Thijssen VL;Mom CH;Kenter GG;Bleeker MCG;de Gruijl TD;Jordanova ES
通讯作者：
Jordanova ES