Dec 7, 2019

Tryptophan 2,3-Dioxygenase Expression Identified in Human Hepatocellular Carcinoma Cells and in Intratumoral Pericytes of Most Cancers

Cancer Immunology Research
Delia HoffmannBenoît J Van den Eynde

Abstract

Tryptophan catabolism is used by tumors to resist immune attack. It can be catalyzed by indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO). IDO1 is frequently expressed in tumors and has been widely studied as a potential therapeutic target to reduce resistance to cancer immunotherapy. In contrast, TDO expression in tumors is not well characterized. Several human tumor cell lines constitutively express enzymatically active TDO. In human tumor samples, TDO expression has previously been detected by transcriptomics, but the lack of validated antibodies has precluded detection of the TDO protein and identification of TDO-expressing cells. Here, we developed novel TDO-specific monoclonal antibodies and confirmed by immunohistochemistry the expression of TDO in the majority of human cancers. In all hepatocarcinomas (10/10), TDO was expressed by most tumor cells. Some glioblastomas (10/39) and kidney carcinomas (1/10) also expressed TDO in tumor cells themselves but only in focal tumor areas. In addition, all cancers tested contained foci of nontumoral TDO-expressing cells, which were identified as pericytes by their expression of PDGFRβ and their location in vascular structures. These TDO-expressing pericytes be...Continue Reading

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Mentioned in this Paper

Tryptophan Catabolic Process
Monoclonal Antibodies
Tryptophan
Immunohistochemistry
Tumor Tissue Sample
Neoplastic Cell
Blood Vessel
Liver Carcinoma
Neoplasms
JM 2820

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