Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma.
Adult
Cells, Cultured
Enzyme Induction
Female
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
/ biosynthesis
Interferon-gamma
/ pharmacology
Kynurenine
/ blood
Male
Melanoma
/ blood
Middle Aged
Monocytes
/ drug effects
Neoplasm Recurrence, Local
Neoplasm Staging
Retrospective Studies
Skin Neoplasms
/ blood
Time Factors
Treatment Outcome
Tryptophan
/ blood
Tumor Escape
IDO1
Kyn/Trp
biomarker
early stage melanoma
immune cells
liquid biopsy
monocytes
tryptophan metabolism
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
07
2021
accepted:
19
08
2021
entrez:
24
9
2021
pubmed:
25
9
2021
medline:
24
12
2021
Statut:
epublish
Résumé
Immune escape is an early phenomenon in cancer development/progression. Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. This study investigated the clinical relevance of IDO1 expression by immune cells in the lymph nodes and blood and of the serum kynurenine/tryptophan (Kyn/Trp) ratio in 65 systemic treatment naïve stage I-III melanoma patients. Blood samples were collected within the first year of diagnosis. Patients had a median follow-up of 61 months. High basal IDO1 expression in peripheral monocytes and low IFNγ-induced IDO1 upregulation correlated with worse outcome independent from disease stage. Interestingly studied factors were not interrelated. During follow-up, the risk of relapse was 9% (2/22) in the subgroup with high IFNγ-induced IDO1 upregulation in monocytes. In contrast, if IDO1 upregulation was low, relapse occurred in 30% (3/10) of patients with low basal IDO1 expression in monocytes and in 61.5% (8/13) in the subgroup with high basal IDO1 expression in monocytes (Log-Rank test, p=0.008). This study reveals some immune features in the blood of early stage melanoma that may be of relevance for disease outcome. These may offer a target for sub-stratification and early intervention.
Identifiants
pubmed: 34557196
doi: 10.3389/fimmu.2021.736498
pmc: PMC8453201
doi:
Substances chimiques
IDO1 protein, human
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Kynurenine
343-65-7
Interferon-gamma
82115-62-6
Tryptophan
8DUH1N11BX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
736498Informations de copyright
Copyright © 2021 Meireson, Ferdinande, Haspeslagh, Hennart, Allorge, Ost, Sundahl, Spaas, Demeyer and Brochez.
Déclaration de conflit d'intérêts
NS reported travel grants from Merck Sharpe & Dohme, Astellas, Bayer and Bristol-Myers Squibb. PO received a research grant from Ferring, Merck, Varian, Bayer, consultancy fees from Ferring, Bayer, Janssen, Sandoz, Sanofi. MH was employed by Dermpat. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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