title: Quality of T-cells after stimulation with leukemia-derived dendritic cells (DC) from patients with acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS) is predictive for their leukemia cytotoxic potential.
abstract: Myeloid leukemic cells can differentiate into leukemia-derived dendritic cells (DC(leu)), presenting known/unknown leukemic-antigens. Induced anti-leukemic T-cell-responses are variable. To further elicit DC/DC(leu)-induced T-cell-response-patterns we performed (functional)flow-cytometry/fluorolysis-assays before/after mixed lymphocyte cultures (MLC) of matched (allogeneic) donor-T-cells (n=6), T-cells prepared at relapse after stem cell transplantation (n=4) or (autologous) patients'-T-cells (n=7) with blast-containing-mononuclear-cells ('MNC') or DC(leu)-containing DC ('DC'). Compared to 'MNC' 'DC' were better mediators of anti-leukaemic T-cell-activity, although not in every case effective. We could define cut-off proportions of mature DC, DC(leu), proliferating, CD4(+), CD8(+) and non-naive T-cells after 'MNC'- or 'DC'-stimulation, that were predictive for an anti-leukemic-activity of stimulated T-cells as well as a response to immunotherapy. Interestingly especially ratios >1 of CD4:CD8 or CD45RO:CD45RA T-cells were predictive for anti-leukemic function after DC-stimulation. In summary the composition and quality of DC and T-cells after a MLC-stimulating-phase is predictive for a successful ex-vivo and in-vivo anti-leukemic response, especially with respect to proportions of proliferating, CD4(+) and CD45RO(+) T-cells. Successful cytotoxicity and the development of a T-cell-memory after 'DC'-stimulation could be predictive for the clinical course of the disease and may pave the way to develop adoptive immunotherapy, especially for patients at relapse after SCT.
authors.affiliation: University of Munich, Department for Haematopoietic Transplantations, Munich, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Liepert
authors.forename: Christine
authors.initials: C
authors.lastname: Grabrucker
authors.forename: Andreas
authors.initials: A
authors.lastname: Kremser
authors.forename: Julia
authors.initials: J
authors.lastname: Dreyssig
authors.forename: Christian
authors.initials: C
authors.lastname: Ansprenger
authors.forename: Markus
authors.initials: M
authors.lastname: Freudenreich
authors.forename: Tanja
authors.initials: T
authors.lastname: Kroell
authors.forename: Roland
authors.initials: R
authors.lastname: Reibke
authors.forename: Johanna
authors.initials: J
authors.lastname: Tischer
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schweiger
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Helga
authors.initials: H
authors.lastname: Schmetzer
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D055815:Young Adult