The development of tailor-made immunotherapy based on ovarian cancer local immunity analysis

• Project/Area Number: 15K10714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Fujita Health University (2017); Nagoya University (2015-2016)
• Principal Investigator: Shibata Kiyoisumi 藤田保健衛生大学, 医学部, 教授 (90335026)
• Co-Investigator(Kenkyū-buntansha): 梶山 広明 名古屋大学, 医学系研究科, 准教授 (00345886)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腹膜播種 / 癌微小環境 / サイトカイン / 卵巣癌 / 微小環境 / ＩＬ－３３ / 免疫療法 / 癌免疫療法

Outline of Final Research Achievements

We aimed to determine the role of cancer-associated mesothelial cells (CAMCs) in the promotion of tumor neovascularization and vascular permeability via enhanced VEGF production and loclal immunologic effects. We examined whether a characteristic morphological change in human peritoneal mesothelial cells (HPMCs) was observed in the presence of malignant ascites and tumor-derived TGF-β. We focused on the enhanced production of VEGF in CAMCs and its crucial role in endothelial tube formation. Ｗe found that EOC-derived TGF-β induced typical EMT-like morphological alteration in HPMCs, which was associated with CAMCs. We further discovered that CAMCs play a crucial role in the enhanced VEGF production.Furethermore we showed that IL-33 secretion was elevated in high metastatic cell lines.The novel mechanism of CAMCs as a facilitator of EOC progression and immnunological effect are displayed by microenvironmental cell-to-cell communication.

Research Products

• [Journal Article] A novel mechanism of neovascularization in peritoneal dissemination via cancer-associated mesothelial cells affected by TGF-β derived from ovarian cancer (2017)
  • Author(s): Fujikake Kayo、Kajiyama Hiroaki、Yoshihara Masato、Nishino Kimihiro、Yoshikawa Nobuhisa、Utsumi Fumi、Suzuki Shiro、Niimi Kaoru、Sakata Jun、Mitsui Hiroko、Shibata Kiyosumi、Senga Takeshi、Kikkawa Fumitaka
  • Journal Title: Oncology Reports Volume: 39 Pages: 193-200
  • DOI: 10.3892/or.2017.6104
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma. (2016)
  • Author(s): Suzuki S, Sakata J, Utsumi F, Sekiya R, Kajiyama H, Shibata K, Kikkawa F, Nakatsura T.
  • Journal Title: Oncoimmunology Volume: 5 Issue: 11 Pages: e1238542-e1238542
  • DOI: 10.1080/2162402x.2016.1238542
  • Peer Reviewed / Open Access
• [Presentation] 卵巣明細胞腺癌に対するGPC3を標的としたペプチドワクチン療法～臨床試験のデータ解析から見える今後の課題～ (2016)
  • Author(s): 柴田清住、鈴木史朗、中面哲也、吉川史隆
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪国際交流センター(大阪府、大阪市）
  • Year and Date: 2016-07-27
• [Presentation] 卵巣明細胞腺癌に対するがん抗原GPC3を標的としたペプチドワクチン療法 (2015)
  • Author(s): 柴田清住
  • Organizer: 第57回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: アイーナいわて県民情報交流センター(岩手県盛岡市）
  • Year and Date: 2015-08-08
  • Invited