Exposure of CD34+ precursors to cytostatic anthraquinone-derivatives induces rapid dendritic cell differentiation: implications for cancer immunotherapy |
| |
Authors: | Rieneke van de Ven Anneke W Reurs Pepijn G J T B Wijnands Sandra van Wetering Ada M Kruisbeek Erik Hooijberg George L Scheffer Rik J Scheper Tanja D de Gruijl |
| |
Institution: | (1) Department of Pathology, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;(2) Division of Immunotherapy, Medical Oncology Laboratory, VU University Medical Center, de Boelelaan 1117-CCA 2.44, 1081 HV Amsterdam, The Netherlands;(3) DCPrime B.V, De Boelelaan 1085 (W&N), 1081 HV Amsterdam, The Netherlands; |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|