Exposure of CD34+ precursors to cytostatic anthraquinone-derivatives induces rapid dendritic cell differentiation: implications for cancer immunotherapy

Appropriate activation of dendritic cells (DC) is essential for successful active vaccination and induction of cell-mediated immunity. The scarcity of precursor cells, as well as long culture methods, have hampered wide-scale application of DC vaccines derived from CD34 + precursors, despite their s...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Vol. 61; no. 2; pp. 181 - 191
Main Authors: van de Ven, Rieneke, Reurs, Anneke W., Wijnands, Pepijn G. J. T. B., van Wetering, Sandra, Kruisbeek, Ada M., Hooijberg, Erik, Scheffer, George L., Scheper, Rik J., de Gruijl, Tanja D.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer-Verlag 01.02.2012
Springer
Springer Nature B.V
Subjects:
Anthracyclines - pharmacology
Anthraquinones - pharmacology
Antigens
Antigens, CD34 - metabolism
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cancer
Cancer Research
Cancer Vaccines
Cell Differentiation
Cell Line
Chemokine CCL19 - metabolism
Chemokine CCL21 - metabolism
Cytostatic Agents - pharmacology
Dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dendritic Cells - pathology
Dendritic Cells - transplantation
Humans
Immunity, Cellular
Immunology
Immunotherapy
Lipopolysaccharide Receptors - metabolism
Medical sciences
Medicine
Medicine & Public Health
Myeloid Progenitor Cells - immunology
Myeloid Progenitor Cells - metabolism
Myeloid Progenitor Cells - pathology
Neoplasms - immunology
Neoplasms - therapy
Oncology
Original
Original Article
Pharmacology. Drug treatments
Vaccines
Netherlands
Dendritic cell
Immunotherapy
precursors
Differentiation
Mitoxantrone
CD34
Cytostatic drugs
Antineoplastic agent
Drug
Anthraquinone derivatives
Cytostatic
Stem cell
Hematopoietic cell
Exposure
Malignant tumor
Cell differentiation
Precursor
Cell subpopulation
Alkylating agent
Treatment
Antimetabolic
Antigen presenting cell
Cancer
ISSN:0340-7004, 1432-0851, 1432-0851
Online Access:Get full text
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Summary:Appropriate activation of dendritic cells (DC) is essential for successful active vaccination and induction of cell-mediated immunity. The scarcity of precursor cells, as well as long culture methods, have hampered wide-scale application of DC vaccines derived from CD34 + precursors, despite their suggested superior efficacy over the more commonly applied monocyte-derived DC (MoDC). Here, employing the CD34 + /CD14 + AML-derived human DC progenitor cell line MUTZ3, we show that cytostatic anthraquinone-derivatives (i.e., the anthracenedione mitoxantrone and the related anthracyclin doxorubicin) induce rapid differentiation of CD34 + DC precursors into functional antigen-presenting cells (APC) in a three-day protocol. The drugs were found to act specifically on CD34 + , and not on CD14 + DC precursors. Importantly, these observations were confirmed for primary CD34 + and CD14 + DC precursors from peripheral blood. Mitoxantrone-generated DC were fully differentiated within three days and after an additional 24 h of maturation, were as capable as standard 9-day differentiated and matured DC to migrate toward the lymph node-homing chemokines CCL19 and CCL21, to induce primary allogeneic T cell proliferation, and to prime functional MART1-specific CD8 + T lymphocytes. Our finding that anthraquinone-derivatives like mitoxantrone support rapid high-efficiency differentiation of DC precursors may have consequences for in vitro production of DC vaccines as well as for novel immunochemotherapy strategies.
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ISSN:0340-7004
1432-0851
1432-0851
DOI:10.1007/s00262-011-1039-x