Therapeutic strategy against bone invasion by oral squmous cell carcinoma tagetting immunosuppressive cells

• Project/Area Number: 26462998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: University of Toyama
• Principal Investigator: Noguchi Makoto 富山大学, 大学院医学薬学研究部(医学), 教授 (50208328)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 口腔癌 / 免疫抑制性細胞 / 抗腫瘍免疫 / マウスモデル / 免疫抑制 / 顎骨浸潤 / 破骨細胞分化

Outline of Final Research Achievements

In the present study, we investigated the mechanism of interaction between Tregs and osteoclasts in a murine model of oral cancer to elucidate the role of Tregs in the bone invasion of oral cancer.SCCVII mouse oral squamous cell carcinoma cells were administered into the C3H/HeN mouse. Tregs were purified from the tumors and cocultured with bone marrow CD11b+ cells in the absence or presence of RANKL and M-CSF for 4 days. Secreted tartrate-resistant acid phosphatase (TRACP) 5b was determined as a marker of osteoclast number. Results: Attenuation of osteoclast-derived TRACP5b was observed in the coculture of tumor derived Tregs and bone marrow CD11b positive cells, and this attenuation of TRACP5b was ameliorated by neutralization of CTLA-4. Conclusions: These results indicate that Tregs may play a protective role in bone invasion of oral cancer via suppression of osteoclast differentiation, and CTLA-4 may be a key regulator for the suppression of osteoclasts by Tregs in oral cancer.

Research Products

• [Journal Article] Gemcitabine chemotherapy induces phenotypic alterations of tumor cells that facilitate antitumor T cell responses in a mouse model of oral cancer. (2014)
  • Author(s): Tomihara Kei
  • Journal Title: Oral Oncology Volume: 50 Issue: 5 Pages: 457-467
  • DOI: 10.1016/j.oraloncology.2014.01.013
  • Peer Reviewed
• [Presentation] CTLA4-mediated inhibition of osteoclastogenesisby regulatory T cells (Tregs) in oral cancer (2016)
  • Author(s): 野口 誠
  • Organizer: 12th Asian Congress on Oral and Maxillofacial Surgery
  • Place of Presentation: Manila, Pilippine
  • Year and Date: 2016-11-09
  • Int'l Joint Research
• [Presentation] CTLA4-mediated inhibition of osteoclastgenesis by regulatory T cells(Tregs) in oral cancer (2014)
  • Author(s): Makoto Noguchi, Kei Tomihara
  • Organizer: 11th Asian Congress on Oral and Maxillofacial Surgery
  • Place of Presentation: 西安市 中国
  • Year and Date: 2014-08-22 – 2014-08-25
• [Presentation] 口腔癌におけるmyeloid derived suppressor cell(MDSC)の機能解析 (2014)
  • Author(s): 冨原 圭、平識 亘、野口 誠
  • Organizer: 第68回日本口腔科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-07 – 2014-05-09