PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response
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,...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/253191 |
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| author | Sara Trabanelli Mariangela Lecciso Valentina Salvestrini Michele Cavo Darina Očadlíková Roberto M. Lemoli Antonio Curti |
| author_facet | Sara Trabanelli Mariangela Lecciso Valentina Salvestrini Michele Cavo Darina Očadlíková Roberto M. Lemoli Antonio Curti |
| author_sort | Sara Trabanelli |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-591510b08fbf4adcbae8a69e8031843d |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-591510b08fbf4adcbae8a69e8031843d2025-08-20T02:05:21ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/253191253191PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune ResponseSara Trabanelli0Mariangela Lecciso1Valentina Salvestrini2Michele Cavo3Darina Očadlíková4Roberto M. Lemoli5Antonio Curti6Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyDepartment of Internal Medicine (DiMI), University of Genoa and IRCCS Azienda Ospedaliera Universitaria S. Martino-IST, 16132 Genoa, ItalyDepartment of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “L. & A. Seràgnoli”, University of Bologna, 40138 Bologna, ItalyIn 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.http://dx.doi.org/10.1155/2015/253191 |
| spellingShingle | Sara Trabanelli Mariangela Lecciso Valentina Salvestrini Michele Cavo Darina Očadlíková Roberto M. Lemoli Antonio Curti PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response Journal of Immunology Research |
| title | PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response |
| title_full | PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response |
| title_fullStr | PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response |
| title_full_unstemmed | PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response |
| title_short | PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response |
| title_sort | pge2 induced ido1 inhibits the capacity of fully mature dcs to elicit an in vitro antileukemic immune response |
| url | http://dx.doi.org/10.1155/2015/253191 |
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