Article
Immune escape in glioblastoma: Interference with dendritic cell differentiation and maturation
Immune Escape-Mechanismen bei malignen Gliomen: Interferenz mit der Differenzierung und Ausreifung dendritischer Zellen
Search Medline for
Authors
Published: | April 23, 2004 |
---|
Outline
Text
Objective
Dendritic cells (DC) are specialized antigen presenting cells, critical to initiation of T-cell responses. Therefore, they are pivotal to anti-tumour immunity. Tumour cells, however, due to permanent immune surveillance, have developed multiple strategies, to evade the immune system, including mechanisms, which interfere with DC function. To identify such immune escape mechanisms in malignant gliomas, interference of the cell lines U373 and A172 with DC differentiation and maturation was studied.
Methods
Monocytes were enriched immunomagnetically to 98.0 ± 0.2% CD14+ purity and cultured under serum-free conditions in the presence of GM-CSF and IL-4 for 6 days, to induced immature DC generation, followed by an additional 3-day culture period in the presence of GM-CSF, IL-4 and TNFα, to induce DC maturation. The effect of glioma cells was determined by addition of conditioned medium (CM) at the onset of cultures (n≥3).
Results
Immature DC showed mainly a CD14- (5.3±2.0%) CD83- (8.4±5.3%) phenotype and revealed potent pinocytosis activity. Presence of U373-CM and A172-CM inhibited down-regulation of the monocyte marker CD14, resulting in 40.8±14.5% and 42.0±3.3% residual CD14+ cells, respectively. Pinocytosis activity of the immature DC was inhibited by 82,0% and 31,6%, respectively. After 9 days of culture, DC had up-regulated the mature DC marker CD83 but lost CD14. In the presence of U373-CM and A172-CM, up-regulation of CD83 was inhibited by 90.1±2.0% and 67.9±19.6%, respectively. Interestingly, this inhibition of DC maturation was not associated with differences in adhesion and co-stimulatory expression. In an initial attempt to identify candidate molecules of immune interference in U373- and A172-CM, Luminex cytokine analysis and cytokine protein array analysis were performed, showing expression of e.g. IL-6, VEGF and TGFβ2, all of which may play a role.
Conclusions
Glioblastoma cells secrete factors, which inhibit DC differentiation and maturation.