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

TitleCritical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsWei J, Xia S, Sun H, Zhang S, Wang J, Zhao H, Wu X, Chen X, Hao J, Zhou X, Zhu Z, Gao X, Gao J-X, Wang P, Wu Z, Zhao L, Yin Z
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume191
Issue1
Pagination500-8
Date Published2013 Jul 1
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.

DOI10.1371/journal.pone.0064663
Alternate JournalJ. Immunol.