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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.
Cell. Immunol. 265, 23-30 (2010)
DOI Verlagsversion bestellen
: Myeloid leukemic cells can differentiate into leukemia-derived dendritic cells (DCleu), presenting known/unknown leukemic-antigens. Induced anti-leukemic T-cell-responses are variable. To further elicit DC/DCleu-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 DCleu-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, DCleu, 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Dendritic cells; Acute myeloid leukemia; Serum-free culture; T-cells; Immunotherapy; Stem cell transplantation
ISSN (print) / ISBN 0008-8749
Zeitschrift Cellular Immunology
Quellenangaben Band: 265, Heft: 1, Seiten: 23-30
Verlagsort San Diego
Begutachtungsstatus Peer reviewed
Institut(e) CCG Hematopoetic Cell Transplants (IMI-KHZ)