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Journal article
Expression of tryptophan 2,3-dioxygenase in metastatic uveal melanoma
Cancers, v 12(2), 405
10 Feb 2020
PMID: 32050636
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment. Here, we have investigated the role of tryptophan 2,3-dioxygenase (TDO) in UM. Both TDO and indoleamine 2,3-dioxygenase (IDO) catalyze tryptophan and produce kynurenine, which could cause inhibition of T cell immune responses. We first studied the expression of TDO on tumor tissue specimens obtained from UM hepatic metastasis. High expression of TDO protein was confirmed in all hepatic metastasis. TDO was positive in both normal hepatocytes and the tumor cells with relatively higher expression in tumor cells. On the other hand, IDO protein remained undetectable in all of the MUM specimens. UM cell lines established from metastasis also expressed TDO protein and increasing kynurenine levels were detected in the supernatant of MUM cell culture. In TCGA database, higher TDO2 expression in primary UM significantly correlated to BAP1 mutation and monosomy 3. These results indicate that TDO might be one of the key mechanisms for resistance to immunotherapy in UM.
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Details
- Title
- Expression of tryptophan 2,3-dioxygenase in metastatic uveal melanoma
- Creators
- Mizue Terai - Sidney Kimmel Cancer CenterEric Londin - Thomas Jefferson UniversityAnkit Rochani - Thomas Jefferson UniversityEmma Link - Drexel UniversityBao Lam - Sidney Kimmel Cancer CenterGagan Kaushal - Thomas Jefferson UniversityAlok Bhushan - Thomas Jefferson UniversityMarlana Orloff - Thomas Jefferson UniversityTakami Sato - Thomas Jefferson University
- Publication Details
- Cancers, v 12(2), 405
- Publisher
- MDPI
- Number of pages
- 14
- Grant note
- Aurore Lebrun Meggie Danielson Thomas Jefferson University (100008513) Eye Melanoma Research Fund Thomas Jefferson University (http://data.elsevier.com/vocabulary/SciValFunders/100008513)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000522477300151
- Scopus ID
- 2-s2.0-85079453375
- Other Identifier
- 991021860773004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology