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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Vydáno v:	Cancer Immunology, Immunotherapy Ročník 61; číslo 2; s. 181 - 191
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Berlin/Heidelberg Springer-Verlag 01.02.2012 Springer Springer Nature B.V
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0340-7004 1432-0851 1432-0851
DOI:	10.1007/s00262-011-1039-x