title: IFN-alpha-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-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with B16alpha 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 B16alpha 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-alpha treatment of B16alpha 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-alpha treatment may induce primarily the truncated isoform of IL-15. Vaccination with irradiated B16alpha 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.
authors.affiliation: Department of Urologic Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Tzu G
authors.initials: TG
authors.lastname: Wu
authors.forename: William A
authors.initials: WA
authors.lastname: Rose
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Albrecht
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Knutson
authors.forename: Rolf
authors.initials: R
authors.lastname: König
authors.forename: Joana R
authors.initials: JR
authors.lastname: Perdigão
authors.forename: Alexandra P A
authors.initials: AP
authors.lastname: Nguyen
authors.forename: W Robert
authors.initials: WR
authors.lastname: Fleischmann
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016898:Interferon-alpha / Q000502:physiology*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D016898:Interferon-alpha; D019409:Interleukin-15