Inhibition of indoleamine 2,3-dioxygenase by stereoisomers of 1-methyl tryptophan in an experimental graft-versus-tumor model.
Exp Hematol
; 42(10): 862-6.e3, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24971697
ABSTRACT
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in tryptophan catabolism that plays an important role in the induction of immune tolerance. Its role in graft-versus-tumor effect after allogeneic stem cell transplantation (allo-SCT) remains unclear. Using a murine graft-versus-tumor model of reduced-intensity allo-HSCT followed by donor leukocyte infusion (DLI), we examined the role of IDO inhibition. Two stereoisomers of 1-methyl tryptophan (1-MT), a small-molecule inhibitor of IDO, reduced the growth of inoculated tumor in the mice that received DLI and had higher expression of IDO1 and IFNγ. However, L-1MT, but not D-1MT, mitigated tumor growth in mice that did not receive DLI and did not express IDO1 and IFNγ. Accordingly, both stereoisomers reduced plasma kynurenine concentrations early after DLI and enhanced in vitro cytotoxic lymphocyte function after allogeneic mixed lymphocyte reaction. Furthermore, L-1MT was more efficient in causing direct cytotoxic effects than D-1MT. Our results suggest that IDO inhibition can benefit anti-tumor therapy in the setting of reduced-intensity allo-SCT using DLI.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triptofano
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Efeito Enxerto vs Tumor
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Mastocitoma
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Indolamina-Pirrol 2,3,-Dioxigenase
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Fatores Imunológicos
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Exp Hematol
Ano de publicação:
2014
Tipo de documento:
Article