IL‐27 enhances the survival of tumor antigen‐specific CD8+ T cells and programs them into IL‐10‐producing, memory precursor‐like effector cells. Issue 2 (15th January 2013)

• Record Type: Journal Article
• Authors: Liu, Zhenzhen; Liu, Jin‐Qing; Talebian, Fatemeh; Wu, Lai‐Chu; Li, Shulin; Bai, Xue‐Feng
• Is Part Of: European journal of immunology. Volume 43:Issue 2(2013:Feb.)
• Page Start: 468
• Page End: 479
• Publication Date: 2013-01-15
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242930
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>