Expression of Tryptophan 2,3-Dioxygenase in Metastatic Uveal Melanoma.
LCMS
TDO
immunotherapy
kynurenine
liver metastatic
metastatic uveal melanoma
tryptophan
tryptophan 2,3- dioxygenase
tumor microenvironment
uveal melanoma
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
10 Feb 2020
10 Feb 2020
Historique:
received:
28
12
2019
revised:
24
01
2020
accepted:
04
02
2020
entrez:
14
2
2020
pubmed:
14
2
2020
medline:
14
2
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32050636
pii: cancers12020405
doi: 10.3390/cancers12020405
pmc: PMC7072257
pii:
doi:
Types de publication
Journal Article
Langues
eng
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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