Balancing CIK Cell Cancer Immunotherapy and PPAR Ligands: One Potential Therapeutic Application for CNS Malignancies.

Autor: Vordermark K; Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of Bonn, Bonn, Germany., Pu J; Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of Bonn, Bonn, Germany., Sharma A; Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of Bonn, Bonn, Germany.; Department of Stereotactic and Functional Neurosurgery, University Hospital of Bonn, Bonn, Germany., Maciacyzk J; Department of Stereotactic and Functional Neurosurgery, University Hospital of Bonn, Bonn, Germany., Schmidt-Wolf IGH; Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of Bonn, Bonn, Germany.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Dec; Vol. 13 (24), pp. e70497.
DOI: 10.1002/cam4.70497
Abstrakt: Background: Cytokine-induced killer (CIK) cell therapy has proven successful in clinical trials regarding glioblastoma. Equally important are the hints suggesting peroxisome proliferator-activated receptors (PPARs) ligands being co-expressed in the central nervous system (CNS). This provides a rationale about investigating the possible synergistic effect of CIK cells and PPARs.
Methodology: We investigated neuroblastoma and glioblastoma cell lines with mature CIK cells and the PPARγ antagonist GW-9662 to assess the effects on cell viability, candidate gene expression (Wnt/β-catenin signalling, DNMT1) and global methylation levels (5-methylcytosine, LINE-1).
Results: Using a clinical applicable PPAR-γ inhibitor, we showed that (1) PPARγ-antagonist GW-9662 suppressed tumor cell growth in both neuroblastoma and glioblastoma cells, (2) PPARγ inhibition had restricted effect on the expression of Wnt/β-catenin associated genes, (3) inhibition of PPARγ led to downregulation of DNMT1 expression, supporting their hypothesized interaction in cancer, (4) a partial modulation of global LINE-1 methylation levels was observed, indicating their role in epigenetic processes, and (5) Combining PPARγ inhibition with CIK cell immunotherapy enhanced cell lysis significantly.
Conclusion: We provide evidence that PPAR ligands in combination with CIK cell immunotherapy could be a valuable option for malignant CNS tumors.
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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