title: IL-27 enhances the survival of tumor antigen-specific CD8+ T cells and programs them into IL-10-producing, memory precursor-like effector cells.
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.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Liu
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Talebian
authors.forename: Lai-Chu
authors.initials: LC
authors.lastname: Wu
authors.forename: Shulin
authors.initials: S
authors.lastname: Li
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D000951:Antigens, Neoplasm; C556062:IL10 protein, mouse; C486767:Il27 protein, mouse; D007378:Interleukins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10