Shedding and immunoregulatory activity of Yac-1 lymphoma cell gangliosides

YAC-1 lymphoma cells, both when cultured in vitro and when passaged in ascites form in vivo, synthesize gangliosides (means of 22.1 and 14.7 nmol lipid-bound sialic acid isolated per 10⁸ cells, respectively) with potent inhibitory effects on mitogen- and antigen-induced lymphoproliferation: 10 to 30 nmol highly purified YAC-1 gangliosides/ml caused >90% inhibition of proliferative responses of murine lymphocytes to concanavalin A, lysozyme (a soluble specific antigen), and allogeneic cells (mixed-lymphocyte response). Measurable quantities of these gangliosides were shed by the tumor cells in vitro and also were recovered from the ascites fluid in vivo. Furthermore, the gangliosides isolated from ascites fluid (mean of 15.3 nmol.ml) had inhibitory activity of a magnitude similar to that of the gangliosides isolated from the tumor cells. Therefore, significant inhibition of normal lymphoproliferative responses by tumor-derived gangliosides occurred at ganglioside concentrations which are actually present in the fluid surrounding the tumor cells in vivo. These results support the hypothesis that shedding of gangliosides may serve to protect tumor cells from host immune destruction.