Next Article in Journal
Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines
Previous Article in Journal
Inhibition of USP9X Downregulates JAK2-V617F and Induces Apoptosis Synergistically with BH3 Mimetics Preferentially in Ruxolitinib-Persistent JAK2-V617F-Positive Leukemic Cells
Open AccessArticle

Expression of Tryptophan 2,3-Dioxygenase in Metastatic Uveal Melanoma

1
Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
2
Computational Medicine Center, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
3
Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, USA
4
College of Medicine, Drexel University, Philadelphia, PA 19129, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 405; https://doi.org/10.3390/cancers12020405
Received: 28 December 2019 / Revised: 24 January 2020 / Accepted: 4 February 2020 / Published: 10 February 2020
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. View Full-Text
Keywords: uveal melanoma; metastatic uveal melanoma; liver metastatic; tryptophan 2,3- dioxygenase; TDO; tryptophan; kynurenine; LCMS; tumor microenvironment; immunotherapy uveal melanoma; metastatic uveal melanoma; liver metastatic; tryptophan 2,3- dioxygenase; TDO; tryptophan; kynurenine; LCMS; tumor microenvironment; immunotherapy
Show Figures

Graphical abstract

MDPI and ACS Style

Terai, M.; Londin, E.; Rochani, A.; Link, E.; Lam, B.; Kaushal, G.; Bhushan, A.; Orloff, M.; Sato, T. Expression of Tryptophan 2,3-Dioxygenase in Metastatic Uveal Melanoma. Cancers 2020, 12, 405.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop