title: Extensive profiling of the expression of the indoleamine 2,3-dioxygenase 1 protein in normal and tumoral human tissues.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ivan
authors.initials: I
authors.lastname: Théate
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: van Baren
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Pilotte
authors.affiliation: Service d'anatomopathologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Moulin
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Larrieu
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hervé
authors.affiliation: Biolibrary, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Gutierrez-Roelens
authors.affiliation: de Duve Institute, Université catholique de Louvain, Brussels, Belgium. Service d'anatomopathologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium. Biolibrary, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.affiliation: Service d'anatomopathologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Sempoux
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium. de Duve Institute, Université catholique de Louvain, Brussels, Belgium. benoit.vandeneynde@bru.licr.org.
authors.forename: Benoît J
authors.initials: BJ
authors.lastname: Van den Eynde
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005836:Genitalia, Female / Q000276:immunology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008207:Lymphatic Metastasis; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009363:Neoplasm Proteins; D012333:RNA, Messenger