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.
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.
Liepert
Anja
A
University of Munich, Department for Haematopoietic Transplantations, Munich, Germany.
Grabrucker
Christine
C
Kremser
Andreas
A
Dreyssig
Julia
J
Ansprenger
Christian
C
Freudenreich
Markus
M
Kroell
Tanja
T
Reibke
Roland
R
Tischer
Johanna
J
Schweiger
Cornelia
C
Schmid
Christoph
C
Kolb
Hans-Jochem
HJ
Schmetzer
Helga
H
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