Melanie Bremm, Sabine Hünecke, Olga Zimmermann, Verena Pfirrmann, Andrea Quaiser, Halvard-Björn Bönig, Jan Sörensen, Thomas Klingebiel, Eva Rettinger, Peter Bader, Claudia Cappel
- Background: Cytokine-induced-killer (CIK) cells are a promising immunotherapeutic approach for impending relapse following hematopoietic stem cell transplantation (HSCT). However, there is a high risk for treatment failure associated with severe graft versus host disease (GvHD) necessitating pharmaceutical intervention post-transplant. Whether immunosuppression with mycophenolate mofetil (MMF) or Ciclosporin A (CsA) influences the cytotoxic effect of CIK cell immunotherapy is still an open issue.
Methods: CIK cells were generated from PBMC as previously described followed by co-incubation with mycophenolic acid (MPA) or CsA. Proliferation, cytotoxicity and receptor expression were investigated following short- (24 h), intermediate- (3 days) and long-term (7 days) MPA incubation with the intention to simulate the in vivo situation when CIK cells were given to a patient with relevant MPA/CsA plasma levels.
Results: Short-term MPA treatment led to unchanged proliferation capacity and barely had any effect on viability and cytotoxic capability in vitro. The composition of CIK cells with respect to T-, NK-like T- and NK cells remained stable. Intermediate MPA treatment lacked effects on NKG2D, FasL and TRAIL receptor expression, while an influence on proliferation and viability was detectable. Furthermore, long-term treatment significantly impaired proliferation, restricted viability and drastically reduced migration-relevant receptors accompanied by an alteration in the CD4/CD8 ratio. CD3+CD56+ cells upregulated receptors relevant for CIK cell killing and migration, whereas T cells showed the most interference through significant reductions in receptor expression. Interestingly, CsA treatment had no significant influence on CIK cell viability and the cytotoxic potential against K562.
Conclusions: Our data indicate that if immunosuppressant therapy is indispensable, efficacy of CIK cells is maintained at least short-term, although more frequent dosing might be necessary.
MetadatenAuthor: | Melanie BremmGND, Sabine HüneckeGND, Olga Zimmermann, Verena PfirrmannGND, Andrea Quaiser, Halvard-Björn BönigORCiDGND, Jan SörensenGND, Thomas KlingebielORCiDGND, Eva RettingerORCiDGND, Peter BaderORCiDGND, Claudia Cappel |
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URN: | urn:nbn:de:hebis:30:3-444025 |
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DOI: | https://doi.org/10.1186/s12967-016-1024-4 |
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ISSN: | 1479-5876 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27620209 |
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Parent Title (English): | Journal of translational medicine |
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Publisher: | BioMed Central |
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Place of publication: | London |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2016 |
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Date of first Publication: | 2016/09/13 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/12/22 |
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Tag: | Allogeneic stem cell transplantation; CIK cells; Immunosuppressive therapy; Immunotherapy; MMF; MPA |
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Volume: | 14 |
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Issue: | Art. 264 |
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Page Number: | 12 |
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First Page: | 1 |
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Last Page: | 12 |
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Note: | © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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HeBIS-PPN: | 427975654 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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