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Mediators of Inflammation
Volume 2014 (2014), Article ID 418292, 12 pages
http://dx.doi.org/10.1155/2014/418292
Research Article

5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity

1Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, Germany
2Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, Germany
3Department for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasße 52, 20246 Hamburg, Germany

Received 6 December 2013; Accepted 28 January 2014; Published 13 March 2014

Academic Editor: Beatrice Gaugler

Copyright © 2014 Thomas Stübig et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.