title: Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells             suppresses tumor growth by promoting natural killer cell accumulation.
abstract: This study examined the role of the immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) in cervical cancer progression and the possible use of this enzyme for cervical cancer therapy. We analyzed IDO protein expression in 9 cervical cancer cell lines (SKG-I, -II, -IIIa, -IIIb, SiHa, CaSki, BOKU, HCS-2 and ME-180) stimulated with interferon-γ. IDO expression was observed in all cell lines except for SKG-IIIb. We transfected the human cervical cancer cell line CaSki that constitutively expresses IDO with a short hairpin RNA vector targeting IDO, and established an IDO-downregulated cell line to determine whether inhibition of IDO mediates cervical cancer progression. IDO downregulation suppressed tumor growth in vivo, without influencing cancer cell growth in vitro. Moreover, IDO downregulation enhanced the sensitivity of cervical 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 cervical cancer progression by activating NK cells, suggesting IDO as a potential therapy for cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine,                     Jichi Medical University, Tochigi, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Sato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.forename: Suzuyo
authors.initials: S
authors.lastname: Takahashi
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; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering; D007371:Interferon-gamma