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High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model

As neoadjuvant and adjuvant chemotherapy schedules often consist of multiple treatment cycles over relatively long periods of time, it is important to know what effects protracted drug administration can have on the immune system. Here, we studied the long-term effects of doxorubicin on the capacity...

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Autores principales: van de Ven, Rieneke, Verbrugge, Sue Ellen, Reurs, Anneke W., Bontkes, Hetty J., Hooijberg, Erik, Jansen, Gerrit, Scheper, Rik J., Scheffer, George L., de Gruijl, Tanja D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119330/
https://www.ncbi.nlm.nih.gov/pubmed/21431918
http://dx.doi.org/10.1007/s00262-011-1003-9
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author van de Ven, Rieneke
Verbrugge, Sue Ellen
Reurs, Anneke W.
Bontkes, Hetty J.
Hooijberg, Erik
Jansen, Gerrit
Scheper, Rik J.
Scheffer, George L.
de Gruijl, Tanja D.
author_facet van de Ven, Rieneke
Verbrugge, Sue Ellen
Reurs, Anneke W.
Bontkes, Hetty J.
Hooijberg, Erik
Jansen, Gerrit
Scheper, Rik J.
Scheffer, George L.
de Gruijl, Tanja D.
author_sort van de Ven, Rieneke
collection PubMed
description As neoadjuvant and adjuvant chemotherapy schedules often consist of multiple treatment cycles over relatively long periods of time, it is important to know what effects protracted drug administration can have on the immune system. Here, we studied the long-term effects of doxorubicin on the capacity of dendritic cell (DC) precursors to differentiate into a particular DC subset, the Langerhans cells (LC). In order to achieve high telomerase activity as detected in hematological stem cells, precursor cells from the acute-myeloid leukemia (AML)-derived cell line MUTZ3 were stably transduced with human telomerase reverse transcriptase (hTERT) to facilitate their growth potential, while preventing growth, and drug-induced senescence, and preserving their unique capacity for cytokine-dependent DC and LC differentiation. The hTERT-MUTZ3 cells were selected with increasing concentrations of the anthracyclin doxorubicin. After 1–2 months of selection with 30–90 nM doxorubicin, the cells completely lost their capacity to differentiate into LC. This inhibition turned out to be reversible, as the cells slowly regained their capacity to differentiate after a 3- to 4-month drug-free period and with this became capable again of priming allogeneic T cells. Of note, the loss and gain of this capacity to differentiate coincided with the loss and gain of a subpopulation within the CD34(+) proliferative compartment with surface expression of the stem cell factor receptor (SCF-R/CD117/c-Kit). These data are in favor of cytostatic drug-free intervals before applying autologous DC-based vaccination protocols, as specific DC precursors may need time to recover from protracted chemotherapy treatment and re-emerge among the circulating CD34(+) hematopoietic stem and precursor cells.
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spelling pubmed-31193302011-07-14 High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model van de Ven, Rieneke Verbrugge, Sue Ellen Reurs, Anneke W. Bontkes, Hetty J. Hooijberg, Erik Jansen, Gerrit Scheper, Rik J. Scheffer, George L. de Gruijl, Tanja D. Cancer Immunol Immunother Original Article As neoadjuvant and adjuvant chemotherapy schedules often consist of multiple treatment cycles over relatively long periods of time, it is important to know what effects protracted drug administration can have on the immune system. Here, we studied the long-term effects of doxorubicin on the capacity of dendritic cell (DC) precursors to differentiate into a particular DC subset, the Langerhans cells (LC). In order to achieve high telomerase activity as detected in hematological stem cells, precursor cells from the acute-myeloid leukemia (AML)-derived cell line MUTZ3 were stably transduced with human telomerase reverse transcriptase (hTERT) to facilitate their growth potential, while preventing growth, and drug-induced senescence, and preserving their unique capacity for cytokine-dependent DC and LC differentiation. The hTERT-MUTZ3 cells were selected with increasing concentrations of the anthracyclin doxorubicin. After 1–2 months of selection with 30–90 nM doxorubicin, the cells completely lost their capacity to differentiate into LC. This inhibition turned out to be reversible, as the cells slowly regained their capacity to differentiate after a 3- to 4-month drug-free period and with this became capable again of priming allogeneic T cells. Of note, the loss and gain of this capacity to differentiate coincided with the loss and gain of a subpopulation within the CD34(+) proliferative compartment with surface expression of the stem cell factor receptor (SCF-R/CD117/c-Kit). These data are in favor of cytostatic drug-free intervals before applying autologous DC-based vaccination protocols, as specific DC precursors may need time to recover from protracted chemotherapy treatment and re-emerge among the circulating CD34(+) hematopoietic stem and precursor cells. Springer-Verlag 2011-03-24 2011 /pmc/articles/PMC3119330/ /pubmed/21431918 http://dx.doi.org/10.1007/s00262-011-1003-9 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Article
van de Ven, Rieneke
Verbrugge, Sue Ellen
Reurs, Anneke W.
Bontkes, Hetty J.
Hooijberg, Erik
Jansen, Gerrit
Scheper, Rik J.
Scheffer, George L.
de Gruijl, Tanja D.
High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model
title High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model
title_full High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model
title_fullStr High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model
title_full_unstemmed High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model
title_short High susceptibility of c-KIT(+)CD34(+) precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model
title_sort high susceptibility of c-kit(+)cd34(+) precursors to prolonged doxorubicin exposure interferes with langerhans cell differentiation in a human cell line model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119330/
https://www.ncbi.nlm.nih.gov/pubmed/21431918
http://dx.doi.org/10.1007/s00262-011-1003-9
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