The quality and quantity of leukemia-derived dendritic cells from patients with acute myeloid leukemia and myelodysplastic syndrome are a predictive factor for the lytic potential of dendritic cells-primed leukemia-specific T cells.
Adoptive immunotherapy is an important therapy option to reduce relapse rates after stem-cell transplantation in patients suffering from acute myeloid leukemia and myelodysplastic syndromes. Myeloid leukemic cells can regularly be induced to differentiate into leukemia-derived dendritic cells (DC(leu)), regaining the stimulatory capacity of professional dendritic cells (DCs) while presenting the known/unknown leukemic antigen repertoire. So far, induced antileukemic T-cell responses are variable or even mediate opposite effects. To further elicit DC/DC(leu)-induced T-cell-response patterns, we generated DC from 17 Acute myeloid leukemia (AML) and 2 myelodysplastic syndrome cases and carried out flowcytometry and (functional) nonradioactive fluorolysis assays before/after mixed lymphocyte cultures 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) ("DC"). Compared with "MNC", "DC" were better mediators of antileukemic-activity, although not in every case effective. We could define DC subtypes and cut-off proportions of DC subtypes/qualities (mature DC/DC(leu)) after "DC" priming, which were predictive for an antileukemic activity of primed T cells and the clinical course of the disease after immunotherapy (allogeneic stem-cell transplantation/donor lymphocytes infusion/therapy). In summary, our data show that the composition and quality of DC after a mixed lymphocyte culture-priming phase is predictive for a successful ex vivo antileukemic response, especially with respect to proportions of mature and leukemia-derived DC. These data contribute not only to predict DC-mediated functions or the clinical course of the diseases but also to develop and refine DC-vaccination strategies that may pave the way to develop and modify adoptive immunotherapy, especially for patients at relapse after allogeneic stem-cell transplantation.
Grabrucker
Christine
C
*Department for Hematopoetic Transplantations, University of Munich, Munich daggerDepartment for Hematology, Municipal Hospital Augsburg, Augsburg section signHelmholtz Center, Munich double daggerMunicipal Hospital Oldenburg, Germany.
Liepert
Anja
A
Dreyig
Julia
J
Kremser
Andreas
A
Kroell
Tanja
T
Freudenreich
Markus
M
Schmid
Christoph
C
Schweiger
Cornelia
C
Tischer
Johanna
J
Kolb
Hans-Jochen
HJ
Schmetzer
Helga
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000951:Antigens, Neoplasm