5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity
Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumo...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/418292 |
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| author | Thomas Stübig Anita Badbaran Tim Luetkens York Hildebrandt Djordje Atanackovic Thomas M. C. Binder Boris Fehse Nicolaus Kröger |
| author_facet | Thomas Stübig Anita Badbaran Tim Luetkens York Hildebrandt Djordje Atanackovic Thomas M. C. Binder Boris Fehse Nicolaus Kröger |
| author_sort | Thomas Stübig |
| collection | DOAJ |
| description | Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and phenotype. Functionality was assessed by a tumor lysis assay. Peripheral blood from patients treated with 5-Aza after alloSCT was monitored for changes in T-cell subpopulations. 5-Aza treatment resulted in a decrease in CD8+ T-cells, whereas CD4+ T-cells increased. Furthermore, numbers of IFN-γ+ T-helper 1 cells (Th1) were reduced, while Treg-cells showed substantial increase. Additionally, CD8+ T-cells exhibited limited killing capacity against leukemic target cells. In vivo data confirm the increase of Treg compartment, while CD8+ T-effector cell numbers were reduced. 5-Aza treatment results in a shift from cytotoxic to regulatory T-cells with a functional phenotype and a major reduction in proinflammatory Th1-cells, indicating a strong inhibition of tumor-specific T-cell immunity by 5-Aza. |
| format | Article |
| id | doaj-art-aa67fc88d1ce46148e67cf1decd8b193 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-aa67fc88d1ce46148e67cf1decd8b1932025-02-03T01:06:55ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/4182924182925-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic ActivityThomas Stübig0Anita Badbaran1Tim Luetkens2York Hildebrandt3Djordje Atanackovic4Thomas M. C. Binder5Boris Fehse6Nicolaus Kröger7Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDepartment of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, GermanyDemethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and phenotype. Functionality was assessed by a tumor lysis assay. Peripheral blood from patients treated with 5-Aza after alloSCT was monitored for changes in T-cell subpopulations. 5-Aza treatment resulted in a decrease in CD8+ T-cells, whereas CD4+ T-cells increased. Furthermore, numbers of IFN-γ+ T-helper 1 cells (Th1) were reduced, while Treg-cells showed substantial increase. Additionally, CD8+ T-cells exhibited limited killing capacity against leukemic target cells. In vivo data confirm the increase of Treg compartment, while CD8+ T-effector cell numbers were reduced. 5-Aza treatment results in a shift from cytotoxic to regulatory T-cells with a functional phenotype and a major reduction in proinflammatory Th1-cells, indicating a strong inhibition of tumor-specific T-cell immunity by 5-Aza.http://dx.doi.org/10.1155/2014/418292 |
| spellingShingle | Thomas Stübig Anita Badbaran Tim Luetkens York Hildebrandt Djordje Atanackovic Thomas M. C. Binder Boris Fehse Nicolaus Kröger 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity Mediators of Inflammation |
| title | 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity |
| title_full | 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity |
| title_fullStr | 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity |
| title_full_unstemmed | 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity |
| title_short | 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity |
| title_sort | 5 azacytidine promotes an inhibitory t cell phenotype and impairs immune mediated antileukemic activity |
| url | http://dx.doi.org/10.1155/2014/418292 |
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