title: Interleukin-17D mediates tumor rejection through recruitment of natural killer cells.
abstract: The process of cancer immunoediting generates a repertoire of cancer cells that can persist in immune-competent hosts. In its most complex form, this process begins with the elimination of highly immunogenic unedited tumor cells followed by the escape of less immunogenic edited cells. Although edited tumors can release immunosuppressive factors, it is unknown whether unedited tumors produce cytokines that enhance antitumor function. Utilizing gene microarray analysis, we found the cytokine interleukin 17D (IL-17D) was highly expressed in certain unedited tumors but not in edited mouse tumor cell lines. Moreover, forced expression of IL-17D in edited tumor cells induced rejection by stimulating MCP-1 production from tumor endothelial cells, leading to the recruitment of natural killer (NK) cells. NK cells promoted M1 macrophage development and adaptive immune responses. IL-17D expression was also decreased in certain high-grade and metastatic human tumors, suggesting that it can be targeted for tumor immune therapy.
authors.affiliation: Department of Pathology, University of California, San Diego, 9500 Gilman Drive MC 0612, La Jolla, CA 92093, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Sullivan
authors.affiliation: Department of Pathology, University of California, San Diego, 9500 Gilman Drive MC 0612, La Jolla, CA 92093, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Saddawi-Konefka
authors.affiliation: Department of Pathology, University of California, San Diego, 9500 Gilman Drive MC 0612, La Jolla, CA 92093, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Gross
authors.affiliation: Department of Biology, University of California, San Diego, 9500 Gilman Drive MC 0612, La Jolla, CA 92093, USA.
authors.forename: Miller
authors.initials: M
authors.lastname: Tran
authors.affiliation: Department of Biology, University of California, San Diego, 9500 Gilman Drive MC 0612, La Jolla, CA 92093, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Mayfield
authors.affiliation: Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Pathology, University of California, San Diego, 9500 Gilman Drive MC 0612, La Jolla, CA 92093, USA. Electronic address: jbui@ucsd.edu.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Bui
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology*; D012509:Sarcoma / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C464462:IL17D protein, human; D020381:Interleukin-17