Leukemia-Derived Immature Dendritic Cells Differentiate into Functionally Competent Mature Dendritic Cells That Efficiently Stimulate T Cell Responses

• Published in: The Journal of immunology (1950) 2004-08, Vol.173 (4), p.2855-2865
• Main Authors: Cignetti, Alessandro, Vallario, Antonella, Roato, Ilaria, Circosta, Paola, Allione, Bernardino, Casorzo, Laura, Ghia, Paolo, Caligaris-Cappio, Federico
• Format: Article
• Language: English
• Subjects: CD40 Ligand - pharmacology; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Movement - immunology; Cells, Cultured; Cytokines - biosynthesis; Cytokines - immunology; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Female; Flow Cytometry; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute - immunology; Lipopolysaccharide Receptors - immunology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Male; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.4.2855

Primary acute myeloid leukemia cells can be induced to differentiate into dendritic cells (DC). In the presence of GM-CSF, TNF-alpha, and/or IL-4, leukemia-derived DC are obtained that display features of immature DC (i-DC). The aim of this study was to determine whether i-DC of leukemic origin could be further differentiated into mature DC (m-DC) and to evaluate the possibility that leukemic m-DC could be effective in vivo as a tumor vaccine. Using CD40L as maturating agent, we show that leukemic i-DC can differentiate into cells that fulfill the phenotypic criteria of m-DC and, compared with normal counterparts, are functionally competent in vitro in terms of: 1) production of cytokines that support T cell activation and proliferation and drive Th1 polarization; 2) generation of autologous CD8(+) CTLs and CD4(+) T cells that are MHC-restricted and leukemia-specific; 3) migration from tissues to lymph nodes; 4) amplification of Ag presentation by monocyte attraction; 5) attraction of naive/resting and activated T cells. Irradiation of leukemic i-DC after CD40L stimulation did not affect their differentiating and functional capacity. Our data indicate that acute myeloid leukemia cells can fully differentiate into functionally competent m-DC and lay the ground for testing their efficacy as a tumor vaccine.