Selim Kuçi, Eva Rettinger, Bernhard Voß, Gerrit Weber, Miriam Stais, Hermann Kreyenberg, Andre Manfred Willasch, Zyrafete Kuçi, Ewa Koscielniak, Stephan Klöß, Dorothee von Laer, Thomas Klingebiel, Peter Bader
- Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and has a poor prognosis. Here we assessed the capability of ex vivo expanded cytokine-induced killer cells to lyse both alveolar and embryonic rhabdomyosarcoma cell lines and investigated the mechanisms involved.
Design and Methods: Peripheral blood mononuclear cells from six healthy donors were used to generate and expand cytokine-induced killer cells. The phenotype and composition of these cells were determined by multiparameter flow cytometry, while their cytotoxic effect against rhabdomyosarcoma cells was evaluated by a europium release assay.
Results: Cytokine-induced killer cells efficiently lysed cells from both rhabdomyosarcoma cell lines. Antibody-mediated masking of either NKG2D molecule on cytokine-induced killer cells or its ligands on rhabdomyosarcoma cells (major histocompatibility antigen related chain A and B and UL16 binding protein 2) diminished this effect by 50%, suggesting a major role for the NKG2D molecule in rhabdomyosarcoma cell killing. No effect was observed after blocking CD11a, CD3 or TCRαβ molecules on cytokine-induced killer cells or CD1d on rhabdomyosar-coma cells. Remarkably, cytokine-induced killer cells used tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to activate caspase-3, as the main caspase responsible for the execution of apoptosis. Accordingly, blocking TRAIL receptors on embryonic rhabdomyosarcoma cell lines significantly reduced the anti-tumor effect of cytokine-induced killer cells. About 50% of T cells within the cytokine-induced killer population had an effector memory phenotype, 20% had a naïve phenotype and approximately 30% of the cells had a central memory phenotype. In addition, cytokine-induced killer cells expressed low levels of activation-induced markers CD69 and CD137 and demonstrated a low alloreactive potential.
Conclusions: Our data suggest that cytokine-induced killer cells may be used as a novel adoptive immunotherapy for the treatment of patients with rhabdomyosarcoma after allogeneic stem cell transplantation.
MetadatenVerfasserangaben: | Selim KuçiORCiDGND, Eva RettingerORCiDGND, Bernhard Voß, Gerrit Weber, Miriam Stais, Hermann KreyenbergORCiDGND, Andre Manfred WillaschORCiDGND, Zyrafete KuçiGND, Ewa KoscielniakORCiD, Stephan KlößGND, Dorothee von LaerORCiDGND, Thomas KlingebielORCiDGND, Peter BaderORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-266005 |
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DOI: | https://doi.org/10.3324/haematol.2009.019885 |
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ISSN: | 1592-8721 |
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ISSN: | 0390-6078 |
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Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/20378565 |
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Titel des übergeordneten Werkes (Englisch): | Haematologica |
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Verlag: | Ferrata Storti Foundation |
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Verlagsort: | Pavia |
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Dokumentart: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Datum der Veröffentlichung (online): | 07.04.2010 |
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Datum der Erstveröffentlichung: | 07.04.2010 |
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Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Datum der Freischaltung: | 13.11.2012 |
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Jahrgang: | 95 |
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Ausgabe / Heft: | 9 |
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Seitenzahl: | 8 |
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Erste Seite: | 1579 |
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Letzte Seite: | 1586 |
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HeBIS-PPN: | 358233682 |
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Institute: | Medizin / Medizin |
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| Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
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DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Lizenz (Deutsch): | Deutsches Urheberrecht |
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