title: Critical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Siyuan
authors.initials: S
authors.lastname: Xia
authors.forename: Huayan
authors.initials: H
authors.lastname: Sun
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Jingya
authors.initials: J
authors.lastname: Wang
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Jianlei
authors.initials: J
authors.lastname: Hao
authors.forename: Xinglong
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Gao
authors.forename: Puyue
authors.initials: P
authors.lastname: Wang
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D007378:Interleukins / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C486767:Il27 protein, mouse; D007378:Interleukins