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Dendritic cells (DC) are critical in the antigen-specific immune response. Suppression of the immune system may contribute to tumorigenesis. A reported mechanism of immune deficiency is due to tumour derived factors. Gangliosides are glycosphingolipids that can be shed by various tumours of neuroectodermal origin and have been shown to have immunosuppressive effects. Neuroblastoma (NBL) is one of the most common extracranial solid tumours in children and patients with advanced disease have a very poor prognosis. Other groups have shown a correlation between tumour burden and increased gangliosides in the periphery of NBL patients. Our preliminary data supports the reported role of gangliosides in the inhibition of monocyte derived DC (MoDC) production from NBL patients in vitro. Monocytes are isolated from the PB of patients and incubated with GM-CSF and IL-4 to produce MoDC, which were harvested and immunophenotyped by flow cytometry on day 7. Addition of the NBL cell line (SK-N-SH) which sheds gangliosides, to MoDC cultures decreased MoDC generation. This was also seen with the addition of a breast tumour cell line (MCF-7), which also sheds gangliosides, indicating that the effect was not primarily due to the NBL cells, but due to a common factor. When normal cells are exposed to gangliosides for 2 hours there was a reduction in MoDC production after 7 days of culture indicating that the effects of gangliosides are long lasting. We also investigated whether DL - threo - 1 - phenyl - 2 - decanolylamine - 3 - morpholino-1-propanol HCl (D-PDMP), an inhibitor of glycosphingolipid synthesis, reversed the effects of gangliosides on monocyte derived DC.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]