平衡 CIK 细胞肿瘤免疫治疗与 PPAR 配体：一种潜在的中枢神经系统恶性肿瘤治疗应用

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).

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.

We provide evidence that PPAR ligands in combination with CIK cell immunotherapy could be a valuable option for malignant CNS tumors.