Immune stimulatory potential of B7.1 and B7.2 retrovirally transduced melanoma cells: suppression by interleukin 10

Abstract

The immunostimulatory capacities of B7.1-and B7.2- expressing melanoma cells were investigated. A365, 960306 and 950504 melanomas, established from nodular melanoma lesions, were retrovirally transduced. Irradiated B7-, B7.1+ and B7.2+ melanoma cells were co-cultured with autologous or allogeneic peripheral blood mononuclear cells (PBMCs). Proliferation was assessed by [3H]thymidine uptake. mRNA encoding for interleukin 2 (IL-2), IL-4, IL-10 and interferon gamma (IFN-gamma) was determined. IFN-gamma, IL-2, IL-4 and IL-10 secretion were quantitated by ELISA. B7.1+ and B7.2+ melanomas induced proliferation of PBMCs and mRNA for IL-2 and IFN-gamma. After co-incubation of transduced melanoma cells with PBMCs, high levels of IL-10 were detectable in the supernatant. The presence of neutralizing anti-IL-10 antibodies resulted in enhanced proliferation and IL-2 and IFN-gamma secretion. Our data indicate that B7.1- and B7.2-transduced melanoma cells trigger lymphocytic proliferation with transcription of IL-10, IL-2 and IFN-gamma. Blocking of IL-10 augments these effects. Gene therapy protocols using tumour cells as a vaccine have to consider the adverse effects of IL-10.