PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response.

Détails

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Etat: Serval
Version: Final published version
ID Serval
serval:BIB_0CBDF1582387
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response.
Périodique
Journal of Immunology Research
Auteur(s)
Trabanelli S., Lecciso M., Salvestrini V., Cavo M., Očadlíková D., Lemoli R.M., Curti A.
ISSN
2314-7156 (Electronic)
ISSN-L
2314-7156
Statut éditorial
Publié
Date de publication
2015
Volume
2015
Pages
253191
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
In the last years, dendritic cells (DC) have been evaluated for antitumor vaccination. Although DC-based vaccines have raised great expectations, their clinical translation has been largely disappointing. For these results, several explanations have been proposed. In particular, the concomitant expression by DCs of tolerogenic pathways, such as the immunosuppressive agent indoleamine 2,3-dioxygenase-1 (IDO1), has been demonstrated. The aim of this study is to evaluate both the stimulatory and the tolerogenic feature of monocyte-derived DCs (Mo-DCs) after maturation with PGE2. In particular, the role of IDO1 expression in PGE2-matured Mo-DCs has been addressed. Here we show that PGE2, which is required for full maturation of DCs, is one mediator of DC tolerance by enhancing IDO1. PGE2-mediated expression of IDO1 results in the production of kynurenine, in the generation of Tregs, and in the inhibition of either the allogeneic or the autologous antigen-specific stimulatory capacity of DCs. When pulsed with leukemic lysates and matured with PGE2, DCs are impaired in the induction of IFN-γ secreting CD4(+) and CD8(+) T cells due to IDO1 upregulation. Moreover, the inhibition of IDO1 enhances the antileukemic response. Overall, these results point toward the use of IDO1 inhibitors to enhance the vaccination capacity of DCs, matured with PGE2.
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/04/2015 19:28
Dernière modification de la notice
08/05/2019 14:20
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