title: Indoleamine-2,3-dioxygenase, an immunosuppressive enzyme that inhibits             natural killer cell function, as a useful target for ovarian cancer therapy.
abstract: This study examined the role of the immuno-suppressive enzyme indoleamine-2,3-dioxygenase (IDO) in ovarian cancer progression, and the possible application of this enzyme as a target for ovarian cancer therapy. We transfected a short hairpin RNA vector targeting IDO into the human ovarian cancer cell line SKOV-3, that constitutively expresses IDO and established an IDO downregulated cell line (SKOV-3/shIDO) to determine whether inhibition of IDO mediates the progression of ovarian cancer. IDO downregulation suppressed tumor growth and peritoneal dissemination in vivo, without influencing cancer cell growth. Moreover, IDO downregulation enhanced the sensitivity of cancer cells to natural killer (NK) cells in vitro, and promoted NK cell accumulation in the tumor stroma in vivo. These findings indicate that downregulation of IDO controls ovarian cancer progression by activating NK cells, suggesting IDO targeting as a potential therapy for ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine,                     Jichi Medical University, Tochigi, Japan.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Naoto
authors.initials: N
authors.lastname: Sato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nonaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering