Indoleamine-2,3-dioxygenase, an immunosuppressive enzyme that inhibits natural killer cell function, as a useful target for ovarian cancer therapy

Wang,Dongdong; Saga,Yasushi; Mizukami,Hiroaki; Sato,Naoto; Nonaka,Hiroaki; Fujiwara,Hiroyuki; Takei,Yuji; Machida,Shizuo; Takikawa,Osamu; Ozawa,Keiya; Suzuki,Mitsuaki

doi:10.3892/ijo.2011.1295

Indoleamine-2,3-dioxygenase, an immunosuppressive enzyme that inhibits natural killer cell function, as a useful target for ovarian cancer therapy

Authors:
- Dongdong Wang
- Yasushi Saga
- Hiroaki Mizukami
- Naoto Sato
- Hiroaki Nonaka
- Hiroyuki Fujiwara
- Yuji Takei
- Shizuo Machida
- Osamu Takikawa
- Keiya Ozawa
- Mitsuaki Suzuki
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Affiliations: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan, Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
Published online on: December 13, 2011 https://doi.org/10.3892/ijo.2011.1295
Pages: 929-934
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

This study examined the role of the immunosuppressive 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.

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