Ganglioside antigens in tissue sections of skin, naevi, and melanoma--implications for treatment of melanoma.
The ganglioside GD3 was distributed widely on melanocytes, naevi, and practically all melanomas. Not all the cells in melanoma appeared to express GD3, so that treatment with MAbs to GD3 could be expected to leave foci of tumor cells resistant to the effects of the MAbs. GM3 had a similar distribution of GD3 on melanoma, but was expressed on a lower percentage of cells in individual tumors. Expression of GM3 appeared to be suppressed on melanoma and naevus cells in the epidermis. Addition of MAbs to GM3 to those against GD3 in the treatment of melanoma may increase the lytic effect against cells coexpressing both gangliosides, but as GM3 did not appear to be expressed on GM3 -ve cells, the percentage of resistant cells may not be decreased. GD2 was expressed on only approximately 25% of primaries and less than 50% of metastases. In individual tumors there was some evidence of reciprocal expression of GD3 and GD2, so the combination of MAbs to GD3 and GD2 may decrease the percentage of melanoma cells that are resistant to either MAb alone. Both GD3 and GD2, but not GM3, was expressed on lymphocytes around melanoma metastases in LNs and around melanomas in skin. GD2 was detected on a large percentage of lymphocytes around metastases in lymph nodes, but not in the skin, suggesting that the gangliosides GD2 and GD3 may be expressed on different subsets of T-lymphocytes. These findings, together with previous studies showing that the MAbs can enhance lymphocyte responses to a variety of stimuli, provide support for the hypothesis that the clinical effects of the MAbs may reflect activation of host responses against the tumor. Further analysis of the role of gangliosides in lymphocyte function is needed.
Hersey
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000941:Antigens / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D005732:Gangliosides / Q000032:analysis / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D009508:Nevus, Pigmented / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D012878:Skin Neoplasms / Q000737:chemistry
D000911:Antibodies, Monoclonal; D000941:Antigens; D000951:Antigens, Neoplasm; D005732:Gangliosides