Investigating cancer-immunoescape mechanism and effective immuunotherapy for ovarian cancer

• Project/Area Number: 25462614
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: Hiroshi Nishio 慶應義塾大学, 医学部, 特任助教 (90445239)
• Co-Investigator(Kenkyū-buntansha): IWATA TAKASHI 慶應義塾大学, 医学部, 専任講師 (30296652) ; 谷口 智憲 慶應義塾大学, 医学部, 助教 (40424163)
• Co-Investigator(Renkei-kenkyūsha): YAGUCHI TOMONORI 慶應義塾大学, 医学部, 助教 (40424163)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 卵巣がん / 免疫逃避 / HNF-1beta / NF-ｋB / STAT3 / 免疫抑制 / サイトカイン

Outline of Final Research Achievements

Cancer-induced immunosuppression is one of the major problems for development of cancer immunotherapies. A transcriptional factor HNF-1β preferentially activated in human ovarian clear cell cancer (OCCC) have been reported. We have investigated roles of HNF-1β in the immunosuppressive activity of human OCCC. HNF-1β knockdown and overexpression experiments revealed that HNF-1β induced immunosuppressive cytokine production. In vitro suppressive activities of human OCCC culture supernatants on dendritic cell were reduced by knockdown of HNF-1β in cancer cells. In the mice model, knockdown of HNF-1β in the cancer cells resulted in restoration of T cell stimulatory activity of murine splenic DC in spleens and tumors. Therefore, HNF-1β activation in human OCCC is an upstream event for induction of immunosuppression, and is an attractive target for restoring immunocompetence in OCCC patients.

Research Products

• [Journal Article] Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer: A 13-Year Experience in a Single Tertiary-Care Center (2016)
  • Author(s): Kasuga Y, Nishio H, Miyakoshi K, Sato S, Sugiyama J, Matsumoto T, Tanaka K, Ochiai D, Minegishi K, Hamatani T, Iwata T, Morisada T, Nakamura M, Fujii T, Kuji N, Aoki D, Tanaka M
  • Journal Title: Int J Gynecol Cancer Volume: 26 Issue: 1 Pages: 163-168
  • DOI: 10.1097/igc.0000000000000571
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy. (2013)
  • Author(s): Kawakami Y, Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Iwata-Kajihara T, Nakamura S, Nishio H, Satomi R, Kobayashi A, Tanaka M, Hoon Park J, Kamijuku H, Tsujikawa T, Kawamura N
  • Journal Title: Ann. N.Y. Acad. Sci., Volume: 1284(1) Issue: 1 Pages: 80-86
  • DOI: 10.1111/nyas.12094
  • Peer Reviewed
• [Journal Article] Reproductive and obstetric outcomes after radical abdominal trachelectomy for early-stage cervical cancer in a series of 31 pregnancies. (2013)
  • Author(s): Nishio H, Fujii T, Sugiyama J, Kuji N, Tanaka M, Hamatani T, Miyakoshi K, Minegishi K, Tsuda H, Iwata T, Tanaka K, Fukuchi T, Takehara Y, Yoshimura Y, Aoki D.
  • Journal Title: Hum Reprod Volume: 28 Issue: 7 Pages: 1793-1798
  • DOI: 10.1093/humrep/det118
  • Peer Reviewed
• [Journal Article] p16(INK4a)immunohistochemistry is a promising biomarker to predict the outcome of low grade cervical intraepithelial neoplasia:comparison study with HPV genotyping (2013)
  • Author(s): Nishio S, Fujii T, Nishio H, Kameyama K, Saito M, Iwata T, Kubushiro K, Aoki D
  • Journal Title: J Gynecol Oncol Volume: 24 Issue: 3 Pages: 215-221
  • DOI: 10.3802/jgo.2013.24.3.215
  • Peer Reviewed
• [Journal Article] 化学療法・分子標的による抗腫瘍免疫応答の制御 (2013)
  • Author(s): 谷口智憲、里見良輔、西尾浩、杉山重里、大村学、川村直、小林明日香、河上裕
  • Journal Title: 実験医学 Volume: 31 Pages: 1938-1944
• [Presentation] 子宮頸がん局所に浸潤するT細胞を用いた免疫療法の開発 (2015)
  • Author(s): Sunthamala Nuchsupha、西尾 浩、谷口 智憲、岩田 卓、河上 裕、青木 大輔
  • Organizer: 婦人科がん分子標的研究会
  • Place of Presentation: 美ヶ原温泉ホテル(長野県松本市）
  • Year and Date: 2015-07-17
• [Presentation] 卵巣明細胞腺癌においてHNF-1βは腫瘍免疫の抑制に関与する (2013)
  • Author(s): 杉山重里、西尾浩、岩田卓、谷口智憲、青木大輔、河上裕
  • Organizer: 第65回日本産科婦人科学会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] ヒト卵巣癌における NF-κB活性化による免疫抑制誘導と NF-κB 阻害剤による改善 (2013)
  • Author(s): 西尾浩、谷口智憲、住本秀敏、梅澤一夫、岩田卓、藤井多久磨、青木大輔、河上裕
  • Organizer: 第72回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] Immunosuppression through HNF-1b signaling in human ovarian clear cell cancer. (2013)
  • Author(s): Hiroshi Nishio1,2, Juri Sugiyama1,2, Tomonori Yaguch1, Takashi Iwata2, Daisuke Aoki2, Yutaka Kawakami1
  • Organizer: /2013/28th Annual meeting of Society for Immunotherapy of Canceｒ
  • Place of Presentation: Gaylord National Hotel & Convention Center(Washington)