Molecular immunotherapy for oral cancer based on the host immunity diagnosis.

• Project/Area Number: 25293412
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Ehime University
• Principal Investigator: Hamakawa Hiroyuki 愛媛大学, 医学(系)研究科(研究院), 教授 (20127905)
• Co-Investigator(Kenkyū-buntansha): Nakashiro Koh-ichi 愛媛大学, 大学院医学系研究科, 准教授 (90314880) ; Goda Hiroyuki 愛媛大学, 医学部付属病院, 講師 (00464371)
• Co-Investigator(Renkei-kenkyūsha): Okamoto Masato 北里大学, 薬学部, 特任教授 (10243718)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 口腔癌 / 免疫療法 / バイオマーカー / IL-6 / 癌間質 / PD-L

Outline of Final Research Achievements

Recently immunotherapy are promising cancer therapy. However, the biomarker evaluating immunological condition is not established. In the present study, We have identified IL-6 and 8 as a critical biomarker in oral cancer. We showed that the serum IL-6 level tended to negatively correlate with favorable outcome. And IL-6 has important roles in cancer progression via angiogenesis. IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages. These findings obtained from this study lead to development of personalized immunochemotherapy for oral cancer patients.

Research Products

• [Journal Article] Prognostic impact of preoperative serum interleukin-6 levels in early stage oral squamous cell carcinoma patients strictly defined by sentinel node biopsy (2016)
  • Author(s): Hiroyuki Goda, Masato Okamoto, Koh-ichi Nakashiro, Satoshi Hino, Ryuichi Murase, Hiroyuki Hamakawa
  • Journal Title: oncology letters Volume: ―
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma (2014)
  • Author(s): Fujita Y, Okamoto M, Goda H, Tano T, Nakashiro K, Sugita A, Fujita T, Koido S, Homma S, Kawakami Y, Hamakawa H.
  • Journal Title: PLoS ONE Volume: 9 Issue: 12 Pages: e110378-e110378
  • DOI: 10.1371/journal.pone.0110378
  • Peer Reviewed / Open Access
• [Journal Article] Immuno-Chemoradiotherapy for Patients with Oral Squamous Cell Carcinoma: Augmentation of OK-432-Induced Helper T-Cell 1 Response by 5-FU and X-Ray Irradiation. (2013)
  • Author(s): Tano T, Okamoto M, Kan S, Bando T, Goda H, Nakashiro K, Shimodaira S, Koido S, Homma S, Fujita T, Sato M, Yamashita N, Hamakawa H, Kawakami Y.
  • Journal Title: Neoplasia Volume: 15(7) Pages: 805-814
  • Peer Reviewed
• [Presentation] Anti-interleukin-6 receptor antibody suppressed oral squamous cell carcinoma by inhibiting tumor-stroma interaction. (2015)
  • Author(s): Hiroyuki Goda, Masato Okamoto, Koh-ichi Nakashiro, Norihiko Tokuzen, Hiroyuki Hamakawa
  • Organizer: ESMO Asia 2015 Congress
  • Place of Presentation: Suntec city, Singapore
  • Year and Date: 2015-12-18
  • Int'l Joint Research
• [Presentation] 口腔扁平上皮癌における腫瘍関連線維芽細胞の臨床的意義 (2015)
  • Author(s): 合田啓之、岡本正人、徳善紀彦、中城公一、浜川裕之
  • Organizer: 第 53 回日本癌治療学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2015-10-29
• [Presentation] Enhancement of the T cell-stimulating ability of dendritic cells by 5-FU via regulation of the expression of ligands for programed cell death 1. (2013)
  • Author(s): Tomoyuki Tano, Masato Okamoto, Hiroyuki Goda, Yohei Fujita, Koh-ichi Nakashiro, and Hiroyuki Hamakawa
  • Organizer: AACR 2013
  • Place of Presentation: Washington, USA
• [Presentation] 口腔扁平上皮癌患者における腫瘍微小環境下での interleukin8 及び CD66b+ 好中球の予後への影響
  • Author(s): 藤田陽平、岡本正人、中城公一、田野智之、合田啓之、藤田知信、河上裕、浜川裕之
  • Organizer: 第 17 回日本がん免疫学会総会
  • Place of Presentation: 宇部市
• [Presentation] 抗癌剤による樹状細胞の免疫抑制分子の制御と T 細胞活性化能の増強：PD-Ls の役割
  • Author(s): 田野智之、岡本正人、合田啓之、藤田陽平、中城公一、浜川裕之
  • Organizer: 第 17 回日本がん免疫学会総会
  • Place of Presentation: 宇部市
• [Presentation] Prognositic impact of infiltration of M2 macrophages to tumorinvasive margin in oral squamous cell carcinoma patients
  • Author(s): 藤田陽平、岡本正人、中城公一、田野智之、合田啓之、藤田知信、河上裕、浜川裕之
  • Organizer: 第 72 回日本癌学会
  • Place of Presentation: 横浜市
• [Presentation] Prognostic impact of sentinel node biopsy and preoperative serum interleukin-6 levels in early stage oral squamous cell carcinoma patients
  • Author(s): Hiroyuki Goda, Masato Okamoto, Koh-ichi Nakashiro, Tomoyuki Tano, Yohei Fujita, Yutaka Kawakami, Hiroyuki Hamakawa
  • Organizer: 21st ICOMS
  • Place of Presentation: Barcelona