Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib.
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Brain Neoplasms
/ drug therapy
Carcinoma, Squamous Cell
/ drug therapy
Cell Line, Tumor
Cyclic N-Oxides
/ pharmacology
Cyclin-Dependent Kinases
/ antagonists & inhibitors
Gene Expression Regulation, Neoplastic
/ drug effects
Glioblastoma
/ drug therapy
Head and Neck Neoplasms
/ drug therapy
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
/ genetics
Indolizines
/ pharmacology
Interferon-gamma
/ pharmacology
Kynurenine
/ metabolism
Metabolic Networks and Pathways
/ drug effects
Neoplasms
/ drug therapy
Pyridinium Compounds
/ pharmacology
Tryptophan
/ metabolism
Tryptophan Oxygenase
/ genetics
IDO1
chemotherapy
solid tumor models
targeted therapy
tryptophan metabolites
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
09
2019
accepted:
09
01
2020
entrez:
3
3
2020
pubmed:
3
3
2020
medline:
23
2
2021
Statut:
epublish
Résumé
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO2) are the key enzymes of tryptophan (TRP) metabolism in the kynurenine pathway (KP). Both enzymes function as indicators of immunosuppression and poor survival in cancer patients. Direct or indirect targeting of either of these substances seems thus reasonable to improve therapy options for patients. In this study, glioblastoma multiforme (GBM) as well as head and neck squamous cell carcinomas (HNSCC) were examined because of their different mechanisms of spontaneous and treatment-induced immune escape. Effects on gene expression and protein levels were examined. Accompanying assessment of TRP metabolites from treated GBM cell culture supernatants was conducted. Our results show a heterogeneous and inversely correlated expression profile of TRP-metabolizing genes among GBM and HNSCC cells, with low, but inducible
Identifiants
pubmed: 32117235
doi: 10.3389/fimmu.2020.00055
pmc: PMC7034242
doi:
Substances chimiques
Cyclic N-Oxides
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Indolizines
0
Pyridinium Compounds
0
Kynurenine
343-65-7
dinaciclib
4V8ECV0NBQ
Interferon-gamma
82115-62-6
Tryptophan
8DUH1N11BX
Tryptophan Oxygenase
EC 1.13.11.11
Cyclin-Dependent Kinases
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55Informations de copyright
Copyright © 2020 Riess, Schneider, Kehnscherper, Gesche, Irmscher, Shokraie, Classen, Wirthgen, Domanska, Zimpfer, Strüder, Junghanss and Maletzki.
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