IFN-α-induced murine B16 melanoma cancer vaccine cells: Induction and accumulation of cell-associated IL-15

Tzu G. Wu, William A. Rose, Thomas B. Albrecht, Eugene P. Knutson, Rolf König, Joana R. Perdigão, Alexandra P.A. Nguyen, William Robert Fleischmann

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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 HL-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 B 16α 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.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2007

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ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Cite this

Wu, T. G., Rose, W. A., Albrecht, T. B., Knutson, E. P., König, R., Perdigão, J. R., Nguyen, A. P. A., & Fleischmann, W. R. (2007). IFN-α-induced murine B16 melanoma cancer vaccine cells: Induction and accumulation of cell-associated IL-15. Journal of Interferon and Cytokine Research, 27(1), 13-22. https://doi.org/10.1089/jir.2007.0039