Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma

Abstract Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue...

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Main Authors: Annika Simone Lück, Jingjing Pu, Ahmad Melhem, Matthias Schneider, Amit Sharma, Ingo G. H. Schmidt-Wolf, Jarek Maciaczyk
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84284-5
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author Annika Simone Lück
Jingjing Pu
Ahmad Melhem
Matthias Schneider
Amit Sharma
Ingo G. H. Schmidt-Wolf
Jarek Maciaczyk
author_facet Annika Simone Lück
Jingjing Pu
Ahmad Melhem
Matthias Schneider
Amit Sharma
Ingo G. H. Schmidt-Wolf
Jarek Maciaczyk
author_sort Annika Simone Lück
collection DOAJ
description Abstract Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue for adoptive cellular immunotherapies in CNS malignancies. Prompt from these findings, herein, we investigated whether dendritic cells (DC) in combination with cytokine-induced killer cells (DC-CIK) could also provide an alternative and more effective way to improve the efficacy of GBM treatment. The analysis showed that DC-CIK cells exerted a significant cytotoxic effect on the glioblastoma cell lines, especially with the phenotype of stem-like cells (GSCs). In addition, the increased specific lysis of these cells subsequent to DC-CIK co-culture was confirmed with confocal fluorescence microscope. The direct interactions between tumor and effector cells were found to be highly effective in GBM organoids (GBOs). Moreover, a significant increase in apoptosis and elevated levels of IFN-γ (and not TNF-α) secretion were observed as a targeting mechanism of DC-CIK cells against GBM cell models. Overall, we provide important preliminary evidence that DC-CIK cells may have potential in the treatment of CNS malignancies, particularly glioblastoma.
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spelling doaj-art-9e30bfef41484364aa045e52951dcfbe2025-01-05T12:21:11ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-024-84284-5Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastomaAnnika Simone Lück0Jingjing Pu1Ahmad Melhem2Matthias Schneider3Amit Sharma4Ingo G. H. Schmidt-Wolf5Jarek Maciaczyk6Department of Stereotactic and Functional Neurosurgery, University Hospital of BonnDepartment of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of BonnDepartment of Neurosurgery, University Hospital BonnDepartment of Neurosurgery, University Hospital BonnDepartment of Stereotactic and Functional Neurosurgery, University Hospital of BonnDepartment of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of BonnDepartment of Stereotactic and Functional Neurosurgery, University Hospital of BonnAbstract Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue for adoptive cellular immunotherapies in CNS malignancies. Prompt from these findings, herein, we investigated whether dendritic cells (DC) in combination with cytokine-induced killer cells (DC-CIK) could also provide an alternative and more effective way to improve the efficacy of GBM treatment. The analysis showed that DC-CIK cells exerted a significant cytotoxic effect on the glioblastoma cell lines, especially with the phenotype of stem-like cells (GSCs). In addition, the increased specific lysis of these cells subsequent to DC-CIK co-culture was confirmed with confocal fluorescence microscope. The direct interactions between tumor and effector cells were found to be highly effective in GBM organoids (GBOs). Moreover, a significant increase in apoptosis and elevated levels of IFN-γ (and not TNF-α) secretion were observed as a targeting mechanism of DC-CIK cells against GBM cell models. Overall, we provide important preliminary evidence that DC-CIK cells may have potential in the treatment of CNS malignancies, particularly glioblastoma.https://doi.org/10.1038/s41598-024-84284-5DC-CIK cellsCytokine-induced killer cellsImmunotherapyGlioblastoma
spellingShingle Annika Simone Lück
Jingjing Pu
Ahmad Melhem
Matthias Schneider
Amit Sharma
Ingo G. H. Schmidt-Wolf
Jarek Maciaczyk
Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
Scientific Reports
DC-CIK cells
Cytokine-induced killer cells
Immunotherapy
Glioblastoma
title Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
title_full Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
title_fullStr Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
title_full_unstemmed Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
title_short Preclinical evaluation of DC-CIK cells as potentially effective immunotherapy model for the treatment of glioblastoma
title_sort preclinical evaluation of dc cik cells as potentially effective immunotherapy model for the treatment of glioblastoma
topic DC-CIK cells
Cytokine-induced killer cells
Immunotherapy
Glioblastoma
url https://doi.org/10.1038/s41598-024-84284-5
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