Transcriptome analysis of tumor microenvironment

• Project/Area Number: 15H06172
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: Taguchi Ayumi 東京大学, 医学部附属病院, 登録研究員 (60756782)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腫瘍内微小環境 / 好中球 / 炎症 / T細胞 / 癌遺伝子 / CXCL10 / KRAS / 免疫 / 卵巣癌 / 免疫細胞 / 癌関連繊維芽細胞 / 腫瘍関連マクロファージ

Outline of Final Research Achievements

Mutant KRAS was transduced into mouse peritoneal cancer model, and tumor formation as well as characteristics of tumor microenvironment was observed. In the KRAS-transduced model, tumor formation was accelerated along with the exaggerated inflammation and increased number of neutrophils. In order to assess the association of neutrophils with peritoneal cancer, neutrophils were depleted with anti-Ly6G antibody. Depletion of neutrophils promoted tumor formation and production of ascites. Depletion of neutrophils decreased CD8 T cells and increased CD4 T cells in ascites. Neutrophils in KRAS-transduced ascites enhanced naive CD8 T cell proliferation with higher level of T cell costimulatory molecule, OX40-L.

Research Products

• [Journal Article] Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis. (2016)
  • Author(s): Yoshida M, Taguchi A, Kawana K, Adachi K, Kawata A, Ogishima J, Nakamura H, Fujimoto A, Sato M, Inoue T, Nishida H, Furuya H, Tomio K, Arimoto T, Koga K, Wada-Hiraike O, Oda K, Nagamatsu T, Kiyono T, Osuga Y, Fujii T
  • Journal Title: Plos One Volume: Aug 2;11 Issue: 8 Pages: e0160330-e0160330
  • DOI: 10.1371/journal.pone.0160330
  • Peer Reviewed / Open Access
• [Journal Article] Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells. (2016)
  • Author(s): Taguchi, A., Koga, K., Kawana, K., Makabe, T., Sue, F., Miyashita, M., Yoshida, M., Urata, Y., Izumi, G., Takamura, M., Harada, M., Hirata, T., Hirota, Y., Wada-Hiraike, O., Fujii, T., Osuga, Y
  • Journal Title: American Journal of Reproductive Immunology Volume: 75 Issue: 4 Pages: 486-492
  • DOI: 10.1111/aji.12489
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Modulation of local and systemic immune responses in the progression of ovarian cancer dissemination (2016)
  • Author(s): Ogishima Juri
  • Organizer: 第７５回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] The role of neutrophils in the course of ovarian cancer progression (2016)
  • Author(s): Yoshida Mitsuyo
  • Organizer: 第７５回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] Cancer cell and oncogene alter subset populations of T and dendritic cells in the tumor microenvironment of disseminated ovarian cancer model (2016)
  • Author(s): Ogishima Juri
  • Organizer: 第６８回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] Oncogenes (KRAS and c-MYC) modulate tumor immune system and enhance peritoneal carcinomatosis in the ovarian cancer (2016)
  • Author(s): Yoshida Mitsuyo
  • Organizer: 第６８回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] 腫瘍免疫における癌原遺伝子(ras、myc)の免疫系への関与と卵巣癌腹腔内進展様式への影響に関する研究 (2015)
  • Author(s): 吉田光代、川名 敬、田口 歩、高橋樹里、中村寛江、藤本麻葉、佐藤雅和、真壁智子、井上知子、山下亜紀、足立克之、長阪一憲、甲賀かをり、織田克利、清野透、大須賀穣、藤井知行
  • Organizer: 第３０回日本生殖免疫学会 総会・学術総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-11-21
• [Presentation] 腹膜癌モデルマウス腹腔内微小環境におけるT細胞、樹状細胞サブセットの検討～癌原遺伝子の獲得免疫系への影響について (2015)
  • Author(s): 高橋樹里、川名敬、田口歩、吉田光代、中村寛江、藤本麻葉、佐藤雅和、井上知子、足立克之、長阪一憲、織田克利、大須賀穣、藤井知行
  • Organizer: 第３０回日本生殖免疫学会 総会・学術総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-11-21
• [Presentation] K-ras and c-myc modulate tumor microenvironment of peritoneal carcinomatosis and enhance its tumorigenesis. (2015)
  • Author(s): Mitsuyo Yoshida, Ayumi Taguchi, Kei Kawana, Kensuke Tomio, Hiroe Nakamura, Asaha Fujimoto，Aki Yamashita, Kazunori Nagasaka, Katsuyuki Adachi, Katsutoshi Oda, Kiyono Toru,Yutaka Osuga, Tomoyuki Fujii
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08