Structural characterization and in vivo immunosuppressive activity of neuroblastoma GD2.
Shedding of neuroblastoma gangliosides is positively correlated with tumour progression in patients with neuroblastoma. In assessing the biological activity of these ganglioside molecules, we recently found that total human neuroblastoma gangliosides inhibit cellular immune responses. Here, we have studied the major neuroblastoma ganglioside, GD2. GD2 was purified by high performance liquid chromatography and structurally characterized by mass spectrometry. Immunoregulatory effects of GD2 in vivo were then determined in an established murine model. GD2 significantly downregulated the local cellular immune response to an allogeneic cell challenge; the usual increase in mass of the lymph node draining the injection site was reduced by 88%, from 1.52 to 0.19 mg (control versus GD2-treated mice; p < 0.01). In parallel, lymphocyte recovery from each node was also reduced from 2.4 to 1.2 x 10(6) cells, and lymphocyte DNA synthesis was reduced to half of the control level. These results show that certain shed tumour gangliosides, such as GD2, function as intercellular signalling molecules, downregulate the cellular immune response, and may thereby enhance tumour formation and progression.
Li
R
R
Center for Cancer and Transplantation Biology, Children's Research Institute, Washington, DC 20010, USA.
Gage
D
D
McKallip
R
R
Ladisch
S
S
D000818:Animals; D002240:Carbohydrate Sequence; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D005732:Gangliosides / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
D005732:Gangliosides; C019403:ganglioside, GD2