IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells

Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1969-74. doi: 10.1073/pnas.0307298101. Epub 2004 Feb 4.


IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8(+) memory T cell survival and proliferation, IL-15 helps maintain a memory CD8(+) T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8(+) T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8(+) T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8(+) T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cells, Cultured
  • Female
  • Humans
  • Immunotherapy
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology*
  • Interleukin-15 / pharmacology
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Melanoma, Experimental / immunology*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Proteins / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • gp100 Melanoma Antigen


  • Interleukin-15
  • Interleukin-2
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Pmel protein, mouse
  • Receptors, Antigen, T-Cell
  • gp100 Melanoma Antigen