Activation of autologous leukemia-specific T cells in acute myeloid leukemia: monocyte-derived dendritic cells cocultured with leukemic blasts compared with leukemia-derived dendritic cells.
In acute myeloid leukemia (AML) blasts can be differentiated into dendritic cell (DC) like cells (AML-DC). These cells have a mature DC-like phenotype, are strong stimulators in mixed leukocyte reactions and can be used to generate leukemia-specific cytotoxic T cells. However, recent reports about naturally existing leukemic DC with immunoregulatory dysfunctions in peripheral blood of AML patients caused concerns about the use of AML-DC for therapeutic purposes. Systematic intra-individual comparisons between AML-DC and non-leukemic DC derived from monocytes (MoDC) in AML patients are missing. Thus, we investigated the ability to generate MoDC from peripheral blood of 17 AML patients in first remission and their functional integrity to stimulate leukemia-specific T cells by simple coculture with leukemic blasts. Phenotypic analysis of AML-DC and MoDC from the same individual patients revealed that MoDC exhibit a more homogenous mature DC phenotype. Additionally, functional analysis demonstrated the ability of remission MoDC to activate autologous leukemia-specific T cells in 11 of 12 patients, whereas AML-DC led to a specific T cell activation in four of eight patients. The presented findings might have impact on the design of further therapeutic studies using autologous antigen-presenting cells.
Molecular Tumor Biology and Tumor Immunology, Department of Internal Medicine I, University Hospital of Cologne, Cologne, Germany.
Andreas
A
Draube
Marc
M
Beyer
Jürgen
J
Wolf
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*