IL-27 enhances the survival of tumor antigen-specific CD8+ T cells and programs them into IL-10-producing, memory precursor-like effector cells

Eur J Immunol. 2013 Feb;43(2):468-79. doi: 10.1002/eji.201242930. Epub 2013 Jan 15.


IL-27 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p40-related protein subunit, EBV-induced gene 3, and a p35-related subunit, p28. IL-27 functions through IL-27R and has been shown to have potent antitumor activity via activation of a variety of cellular components, including antitumor CD8(+) T-cell responses. However, the exact mechanisms of how IL-27 enhances antitumor CD8(+) T-cell responses remain unclear. Here we show that IL-27 significantly enhances the survival of activated tumor antigen-specific CD8(+) T cells in vitro and in vivo, and programs tumor antigen-specific CD8(+) T cells into memory precursor-like effector cells, characterized by upregulation of Bcl-6, SOCS3, Sca-1, and IL-10. While STAT3 activation and the CTL survival-enhancing effects can be independent of CTL IL-10 production, we show here that IL-27-induced CTL IL-10 production contributes to memory precursor cell phenotype induction, CTL memory, and tumor rejection. Thus, IL-27 enhances antitumor CTL responses via programming tumor antigen-specific CD8(+) T cells into a unique memory precursor type of effector cells characterized by a greater survival advantage. Our results have important implications for designing immunotherapy against human cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cell Survival / immunology
  • Immunologic Memory / immunology*
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Up-Regulation / immunology


  • Antigens, Ly
  • Antigens, Neoplasm
  • IL10 protein, mouse
  • Il27 protein, mouse
  • Interleukins
  • Ly6a protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • STAT3 Transcription Factor
  • Socs3 protein, mouse
  • Stat3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interleukin-10