IFN-α-Induced Murine B16 Melanoma Cancer Vaccine Cells: Induction and Accumulation of Cell-Associated IL-15

Abstract

Long-term treatment of mouse cancer cells with interferon-α (IFN-α) converts parental B16 melanoma cells to B16α vaccine cells. Inoculation of syngeneic mice with B16α vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and natural killer (NK) cells. Lymph node cells from mice inoculated with irradiated B16α vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Long-term IFN-α treatment of B16α vaccine cells induced both interleukin-15 (IL-15) mRNA and IL-15 protein. The bulk of the induced IL-15 remained cell associated, either cytoplasmic or associated with the cell membrane. Immunofluorescence microscopy studies showed that the cell-associated IL-15 was broadly distributed throughout the cytoplasm. These observations suggest that long-term IFN-α treatment may induce primarily the truncated isoform of IL-15. Vaccination with irradiated B16α vaccine cells may promote tumor immunity by releasing high levels of cell-associated IL-15 when spontaneously lysed or directly killed by innate immune cells. The release of accumulated cell-associated IL-15 may then trigger a host T cell response to tumor antigens and cause host development of immunity to the B16 tumor cells.