Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia

• Published in: Cancer immunity Vol. 3; p. 8
• Main Authors: Li, Li, Schmitt, Anita, Reinhardt, Peter, Greiner, Jochen, Ringhoffer, Mark, Vaida, Bianca, Bommer, Martin, Vollmer, Markus, Wiesneth, Markus, Döhner, Hartmut, Schmitt, Michael
• Format: Journal Article
• Language: English
• Published: United States 16.07.2003
• Subjects: Acute Disease; Adult; Aged; Aged, 80 and over; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; B7-1 Antigen - biosynthesis; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-2 Antigen; CD40 Antigens - biosynthesis; CD40 Antigens - immunology; CD40 Antigens - metabolism; Cell Communication - physiology; Cell Differentiation - physiology; Cell Line; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Dendritic Cells - ultrastructure; DNA, Complementary - genetics; Female; HLA-DR Antigens - biosynthesis; HLA-DR Antigens - immunology; Humans; Immunophenotyping - methods; K562 Cells; Leukemia, Myeloid - immunology; Leukemia, Myeloid - pathology; Male; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - immunology; Microscopy, Electron, Scanning; Middle Aged; Monocytes - chemistry; Monocytes - metabolism; Neoplastic Stem Cells - chemistry; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - physiology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - physiology; T-Lymphocytes - ultrastructure; Tumor Cells, Cultured
• ISSN: 1424-9634

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.