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 view of its expression in normal and tumor tissues is still required in order to anticipate the risks and potential benefits of IDO1 inhibitors. Using a new 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 placenta and lung, and by epithelial cells in the female genital tract. It was also expressed in lymphoid tissues, in cells with a phenotype of mature dendritic cells (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. These cells were tumor cells, endothelial cells and stromal cells, in proportions that varied depending on the tumor type. Tumors showing the highest proportions of IDO1-immunolabelled samples included carcinomas of endometrium and cervix, followed by kidney, lung, and colon. This hierarchy was confirmed by gene expression data mined from the TCGA database. Our observations indicate that the relevant IDO1 for tumoral immune escape is expressed in the tumor itself rather than in its draining lymph node. They also help selecting the most likely tumors to benefit from targeted therapy with IDO1 inhibitors.
- Received July 18, 2014.
- Revision received September 16, 2014.
- Accepted September 16, 2014.
- Copyright © 2014, American Association for Cancer Research.