Critical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells.

Critical roles of IL-27 in autoimmune diseases and infections have been reported; however, the contribution of endogenous IL-27 to tumor progression remains elusive. In this study, by using IL-27p28 conditional knockout mice, we demonstrate that IL-27 is critical in protective immune response against methyl-cholanthrene-induced fibrosarcoma and transplanted B16 melanoma, and dendritic cells (DCs) are the primary source. DC-derived IL-27 is required for shaping tumor microenvironment by inducing CXCL-10 expression in myeloid-derived suppressor cells and regulating IL-12 production from DCs, which lead to the recruitment and activation of NK and NKT cells resulting in immunological control of tumors. Indeed, reconstitution of IL-27 or CXCL-10 in tumor site significantly inhibits tumor growth and restores the number and activation of NK and NKT cells. In summary, our study identifies a previous unknown critical role of DC-derived IL-27 in NK and NKT cell-dependent antitumor immunity through shaping tumor microenvironment, and sheds light on developing novel therapeutic approaches based on IL-27.

Citation

Jun Wei, Siyuan Xia, Huayan Sun, Song Zhang, Jingya Wang, Huiyuan Zhao, Xiaoli Wu, Xi Chen, Jianlei Hao, Xinglong Zhou, Zhengmao Zhu, Xiang Gao, Jian-xin Gao, Puyue Wang, Zhenzhou Wu, Liqing Zhao, Zhinan Yin. Critical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells. Journal of immunology (Baltimore, Md. : 1950). 2013 Jul 1;191(1):500-8

Mesh Tags

Substances

PMID: 23733881

search → result