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

Authors

  • Zhenzhen Liu,

    1. Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
    2. Ohio State Biochemistry Program, Columbus, OH, USA
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  • Jin-Qing Liu,

    1. Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
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  • Fatemeh Talebian,

    1. Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
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  • Lai-Chu Wu,

    1. Ohio State Biochemistry Program, Columbus, OH, USA
    2. Davis Medical Center, Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA
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  • Shulin Li,

    1. Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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  • Xue-Feng Bai

    Corresponding author
    1. Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
    • Full Correspondence: Dr. Xue-Feng Bai, Department of Pathology and Comprehensive Cancer Center, The Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA

      Fax: +1-614-292 7072

      e-mail: Xue-Feng.Bai@osumc.edu

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Abstract

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.

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