title: Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
abstract: Acute myeloid leukemia (AML) is a clonal disease of hematopoiesis with poor clinical outcome despite recent improvements in chemotherapy and stem cell transplantation regimens. Immunotherapy with dendritic cells (DCs) eliciting specific T cell responses to leukemia-associated antigens (LAAs) might be a therapeutic option. DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts. The expression of these antigens on DCs generated from 15 AML patients (AML-DCs) and on DCs generated from 15 healthy volunteers (HV-DCs) was analyzed by FACS. All DCs displayed the typical morphology and tested negative for B, T and NK cell markers. The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts. Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs. HLA-ABC was preserved on AML-DCs (median 95%). Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs. AML-DCs express at least one LAA and strongly express HLA and costimulatory molecules, the prerequisites for eliciting T cell responses. AML-DCs may play a role in vaccine-based immunotherapies for AML patients.
authors.affiliation: Third Department of Internal Medicine, University of Ulm, Ulm, Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Peter
authors.initials: P
authors.lastname: Reinhardt
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Mark
authors.initials: M
authors.lastname: Ringhoffer
authors.forename: Bianca
authors.initials: B
authors.lastname: Vaida
authors.forename: Martin
authors.initials: M
authors.lastname: Bommer
authors.forename: Markus
authors.initials: M
authors.lastname: Vollmer
authors.forename: Markus
authors.initials: M
authors.lastname: Wiesneth
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D018076:DNA, Complementary; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins