Mechanisms of tumor-induced immune tolerance during the process of peritoneal dissemination of ovarian cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Wakayama Medical University
• Principal Investigator: INO Kazuhiko 和歌山県立医科大学, 医学部, 教授 (60303640)
• Co-Investigator(Kenkyū-buntansha): MABUCHI Yasushi 和歌山県立医科大学, 医学部, 助教 (80382357)
• Project Period (FY): 2011 – 2013
• Keywords: 卵巣癌 / 腫瘍免疫 / 免疫寛容 / 腹膜播種 / マウスモデル / 酵素

Research Abstract

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. IDO-cDNA was transfected into the murine ovarian carcinoma cell line HM-1, establishing IDO-overexpressing cells (HM-1-IDO). HM-1-IDO or mock were intraperitoneally transplanted into syngeneic immunocompetent mice. HM-1-IDO-transplanted mice showed significantly shortened survival, and increased tumor weight and ascites with the significantly reduced numbers of CD8+ T cells and NK cells within tumors as well as increased levels of TGF-beta in ascites. These data show that tumoral IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating T and NK-cell recruitment and enhancement of immunosuppressive cytokines in ascites, thus IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.

Research Products

• [Journal Article] Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer via inducing immunosuppressive environment (2014)
  • Author(s): Tanizaki Y, Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K
  • Journal Title: Cancer Sci
  • DOI: 10.1111/cas.12445.
• [Journal Article] Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer (2014)
  • Author(s): Tanizaki Y, Kobayashi A, Shiro M, Ota N, Takano R, Mabuchi Y, Yagi S, Minami S, Terada M, Ino K
  • Journal Title: Int J Gynecol Cancer Volume: 24(3) Pages: 454-60
  • DOI: 10.1097/IGC.0000000000000074.
• [Journal Article] Monoclonality of composite large-cell neuroendocrine carcinoma and invasive intestinal-type mucinous adenocarcinoma of the cervix : a case study (2013)
  • Author(s): Yasuoka H, Tsujimoto M, Ueda M, Kodama R, Iwahashi Y, Inagaki M, Mabuchi Y, Ino K, Sanke T, Nakamura Y
  • Journal Title: Int J Gynecol Pathol Volume: 32(4) Pages: 416-20
  • DOI: 10.1097/PGP.0b013e318261c35b
• [Journal Article] Clinicopathological significance of podocalyxin and phosphorylated ezrin in uterine endometrioid adenocarcinoma (2012)
  • Author(s): Yasuoka H, Tsujimoto M, Inagaki M, Kodama R, Tsuji H, Iwahashi Y, Mabuchi Y, Ino K, Sanke T, Nakamura Y
  • Journal Title: J Clin Pathol Volume: 65(5) Pages: 399-402
  • DOI: 10.1136/jclinpath-2011-200359
• [Journal Article] Role of the renin-angiotensin system in gynecologic cancers (2011)
  • Author(s): Ino K, Shibata K, Yamamoto E, Kajiyama H, Nawa A, Mabuchi Y, Yagi S, Minami S, Tanizaki Y, Kobayashi A, Kikkawa F
  • Journal Title: Curr Cancer Drug Targets Volume: 11(4):. Pages: 405-11
• [Journal Article] Indoleamine 2,3-dioxygenase and immune tolerance in ovarian cancer (2011)
  • Author(s): Ino K
  • Journal Title: Curr Opin Obstet Gynecol Volume: 23(1) Pages: 13-8
  • DOI: 10.1097/GCO.0b013e3283409c79
• [Presentation] Suppression of STAT1 signal pathways reduces ovarian cancer progression (2013)
  • Author(s): Aya Kobayashi, Yuko Tanizaki, Saori Toujima, Tamaki Yahata, Madoka Yamamoto, Michihisa Shiro, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi, Sawako Minami, Toshikazu Kondo, Kazuhiko Ino
  • Organizer: The 3rd ASGO / The 55th JSGO
  • Place of Presentation: Kyoto
  • Year and Date: 20131213-15
• [Presentation] Pivotal roles of CX3CL1-CX3CR1 axis on host cells in ovarian cancer progression (2013)
  • Author(s): Yuko Tanizaki, Aya Kobayashi, Saori Toujima, Tamaki Yahata, Madoka Yamamoto, Michihisa Shiro, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi, Sawako Minami, Toshikazu Kondo, Kazuhiko Ino
  • Organizer: The 3rd ASGO / The 55th JSGO
  • Place of Presentation: Kyoto
  • Year and Date: 20131213-15
• [Presentation] 免疫寛容を誘導するIndoleamine 2,3-dioxygenaseは卵巣癌腹膜播種を促進し、新規標的治療の候補分子になり得る (2012)
  • Author(s): 谷﨑優子、小林彩、東嶋左緒里、山本円、馬淵泰士、八木重孝、岩橋正明、南佐和子、井箟一彦
  • Organizer: 第11回婦人科がん分子標的研究会
  • Place of Presentation: 日光.
  • Year and Date: 20120600
• [Presentation] 免疫寛容誘導分子IDOは卵巣癌腹膜播種を促進する (2012)
  • Author(s): 谷崎優子、小林彩、山本円、馬淵泰士、岩橋正明、南佐和子、井箟一彦
  • Organizer: 第64回日本産科婦人科学会
  • Place of Presentation: 神戸
  • Year and Date: 20120400