title: Anti-leukemia T cells in AML: TNF-α⁺ CD8⁺ T cells may escape detection and possibly reflect a stage of functional impairment.
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-α secretion has previously been described. The aim of this study was to investigate whether these TNF-α(+)/IFN-γ(-) 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-γ(+)/TNF-α(+), (2) IFN-γ(+)/TNF-α(-), (3) TNF-α(+)/IFN-γ(-) and (4) IFN-γ(-)/TNF-α(-). TNF-α(+)/IFN-γ(-) 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-α(+)/IFN-γ(-) CD8(+) T-cells needs further investigations.
authors.affiliation: Department of Hematology; Oncology, and Tumor Immunology; Charité University Medicine Berlin, Campus Virchow-Klinikum and Campus Benjamin Franklin; Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
authors.forename: Antje
authors.initials: A
authors.lastname: van Lessen
authors.forename: Theis H
authors.initials: TH
authors.lastname: Terwey
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Renate
authors.initials: R
authors.lastname: Arnold
authors.forename: Antonio
authors.initials: A
authors.lastname: Pezzutto
authors.forename: Jörg
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D025721:WT1 Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; D025721:WT1 Proteins; C583751:WT1 protein, human; D053146:Myeloblastin
keywords: AML; IFN-γ; T cell response; TNF-α; cytokine profile