Extensive Profiling of the Expression of the Indoleamine 2,3-Dioxygenase 1 Protein in Normal and Tumoral Human Tissues
Extensive Profiling of the Expression of the Indoleamine 2,3-Dioxygenase 1 Protein in Normal and Tumoral Human Tissues
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DOI：
10.1158/2326-6066.cir-14-0137
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发表时间：
2015-02-01
影响因子：
10.1
通讯作者：
Van den Eynde, Benoit J.
中科院分区：
文献类型：
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作者：
Theate, Ivan;van Baren, Nicolas;Van den Eynde, Benoit J.
吲哚胺2,3-双加氧酶1 （IDO1）的色氨酸分解代谢在肿瘤免疫排斥抵抗中起关键作用。在人类中，已在几种肿瘤类型中观察到IDO1的组成性表达。然而，仍需要对其在正常和肿瘤组织中的表达进行全面分析，以预测IDO1抑制剂的风险和潜在益处。使用一种新验证的人IDO1单克隆抗体，我们对正常和肿瘤组织中IDO1的表达进行了广泛的免疫组织化学分析。在正常组织中，IDO1通过胎盘和肺的内皮细胞以及女性生殖道的上皮细胞表达。在淋巴组织中，IDO1在成熟树突状细胞中表达，其表型（CD83（+）、DC-LAMP（+）、langerin（+）、CD123（+）、CD163(+)）与浆细胞样树突状细胞不同。重要的是，与先前报道的结果相反，表达ido1的树突状细胞在肿瘤引流淋巴结中并不富集。在大部分（505/866,58%）的人类肿瘤中发现了表达ido1的细胞。它们由肿瘤细胞、内皮细胞和基质细胞组成，其比例取决于肿瘤类型。显示ido1免疫标记样本比例最高的肿瘤是子宫内膜癌和子宫颈癌，其次是肾癌、肺癌和结肠癌。从癌症基因组图谱数据库中挖掘的基因表达数据证实了IDO1表达的层次结构。IDO1的表达可用于选择可能受益于IDO1抑制剂靶向治疗的肿瘤。(c) 2014年aacr。
Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tumoral resistance to immune rejection. In humans, constitutive expression of IDO1 has been observed in several tumor types. However, a comprehensive analysis of its expression in normal and tumor tissues is still required to anticipate the risks and potential benefits of IDO1 inhibitors. Using a newly validated monoclonal antibody to human IDO1, we performed an extensive immunohistochemical analysis of IDO1 expression in normal and tumor tissues. In normal tissues, IDO1 was expressed by endothelial cells in the placenta and lung and by epithelial cells in the female genital tract. In lymphoid tissues, IDO1 was expressed in mature dendritic cells with a phenotype (CD83(+), DC-LAMP(+), langerin(+), CD123(+), CD163(+)) distinct from plasmacytoid dendritic cells. Importantly, IDO1-expressing dendritic cells were not enriched in tumor-draining lymph nodes, in contrast with previously reported findings. IDO1-expressing cells were observed in a large fraction (505/866, 58%) of human tumors. They comprised tumor cells, endothelial cells, and stromal cells in proportions that varied depending on the tumor type. Tumors showing the highest proportions of IDO1-immunolabeled samples were carcinomas of the endometrium and cervix, followed by kidney, lung, and colon. This hierarchy of IDO1 expression was confirmed by gene expression data mined from The Cancer Genome Atlas database. Expression of IDO1 may be used to select tumors likely to benefit from targeted therapy with IDO1 inhibitors. (C) 2014 AACR.