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Anti-leukemia T cells in AML: TNF-α(+) CD8(+) T cells may escape detection and possibly reflect a stage of functional impairment

Item Type:Article
Title:Anti-leukemia T cells in AML: TNF-α(+) CD8(+) T cells may escape detection and possibly reflect a stage of functional impairment
Creators Name:Flörcken, A. and van Lessen, A. and Terwey, T.H. and Dörken, B. and Arnold, R. and Pezzutto, A. and Westermann, J.
Abstract:Leukemia-associated antigens such as proteinase-3 (PR3) and Wilms' tumor protein-1 (WT-1) are potential targets of T-cell responses, which can be monitored by T-cell assays within vaccination trials and after allogeneic stem cell transplantation (SCT). In chronic myeloid leukemia (CML) an aberrant cytokine profile of antigen-specific T-cells with predominant TNF-{alpha} secretion has previously been described. The aim of this study was to investigate whether these TNF-{alpha}(+)/IFN-{gamma}(-) CD8(+) T-cells can also be observed in AML patients after SCT. Eight HLA-A2(+) AML patients at different time points after SCT were evaluated for HLA-A2-restricted CD8(+) T-cell responses against PR3, WT-1 and influenza-A using pentamer staining and different cytokine-based T-cell assays. Antigen-specific T-cell immune responses against influenza-A and PR3 were observed in 4/8 patients, WT-1-specific T-cells could be detected in 3/8 patients. Interestingly, four different cytokine secretion profiles of antigen-specific T-cells were detected: (1) IFN-{gamma}(+)/TNF-{alpha}(+), (2) IFN-{gamma}(+)/TNF-{alpha}(-), (3) TNF-{alpha}(+)/IFN-{gamma}(-) and (4) IFN-{gamma}(-)/TNF-{alpha}(-). TNF-{alpha}(+)/IFN-{gamma}(-) CD8(+) T-cells are an interesting biological phenomenon which can obviously be observed also in AML patients. This finding has important implications for both T-cell biology and monitoring within immunotherapy trials. The functional characterization of these TNF-{alpha}(+)/IFN-{gamma}(-) CD8(+) T-cells needs further investigations.
Keywords:AML, IFN-{gamma}, T Cell Response, TNF-{alpha}, Cytokine Profile
Source:Human Vaccines & Immunotherapeutics
Publisher:Landes Bioscience
Page Range:1200-1204
Date:1 June 2013
Official Publication:https://doi.org/10.4161/hv.24250
PubMed:View item in PubMed

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