Establishment of a method for immunostimulation to compensate gene polymorphism-associated deterioration of NK cell function

• Project/Area Number: 15K15476
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: Hideki Ohdan 広島大学, 医歯薬保健学研究院(医), 教授 (10363061)
• Co-Investigator(Kenkyū-buntansha): 田中 友加 広島大学, 医歯薬保健学研究院(医), 准教授 (90432666)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); 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: 免疫賦活療法 / NK細胞 / 個別化医療 / 癌免疫 / 自然免疫

Outline of Final Research Achievements

The aim of this study is to establish a method for immunostimulation to compensate gene polymorphism-associated deterioration of NK cell function. In mouse models, we found that heat shock protein (HSP)70 inducer enhance the expression of TRAIL on live NK cells. We investigated the effects of epigenetic drugs on immunogenicity of neoplastic cells and function of NK cells by use of clinical specimens and human lymphocytes. In addition, we found that ex vivo licensing NK cells developed from hematopoietic stem cells for adoptive immunotherapy was feasible by cultivating them with HLA class I-KIR matched fibroblasts.

Research Products

• [Journal Article] Fc-gamma receptor 3A polymorphism predicts the incidence of urinary tract infection in kidney-transplant recipients. (2017)
  • Author(s): Lalit Kumar Das, Kentaro Ide, Asuka Tanaka, Hiroshi Morimoto, Seiichi Shimizu, Naoki Tanimine, Yuka Tanaka, Hideki Ohdan
  • Journal Title: Human Immunology Volume: 78 Issue: 4 Pages: 357-362
  • DOI: 10.1016/j.humimm.2017.03.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates. (2017)
  • Author(s): Tanimine N, Tanaka Y, Abe T, Piao J, Ishiyama K, Kobayashi T, Ide K, Ohira M, Tahara H, Shimizu S, Saeki Y, Sakai H, Yano T, Ohdan H.
  • Journal Title: Transplant Proceedings Volume: 49 Issue: 1 Pages: 98-101
  • DOI: 10.1016/j.transproceed.2016.11.020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fc-Gamma Receptor Polymorphisms Predispose Patients to Infectious Complications After Liver Transplantation. (2016)
  • Author(s): Shimizu S, Tanaka Y, Tazawa H, Verma S, Onoe T, Ishiyama K, Ohira M, Ide K, Ohdan H.
  • Journal Title: Am J Transplant. Volume: 16(2) Issue: 2 Pages: 625-633
  • DOI: 10.1111/ajt.13492
  • Peer Reviewed
• [Journal Article] Functional Behavior of NKp46-Positive Intrahepatic Natural Killer Cells Against Hepatitis C Virus Reinfection After Liver Transplantation. (2016)
  • Author(s): Tanimine N, Tanaka Y, Abe T, Piao J, Chayama K, Ohdan H.
  • Journal Title: Transplantation Volume: 100(2) Issue: 2 Pages: 355-364
  • DOI: 10.1097/tp.0000000000001031
  • Peer Reviewed
• [Presentation] Corticosteroids dampen Natural Killer cell function including cytotoxicity and anti-HCV effect (2016)
  • Author(s): Ohira M, Hotta R, Yano T, Nakano R, Tzakis A, Nishida S, Ohdan H.
  • Organizer: Asian Transplantation Week 2016
  • Place of Presentation: Inchon, Korea
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] 肝移植術後重症感染症における自然免疫遺伝子多型に対するドナー肝由来活性化NK細胞療法の有用性 (2016)
  • Author(s): 清水誠一, 田中友加, 大平真裕, 石山宏平, 井手健太郎, 田原裕之, 佐伯吉弘, 坂井寛, 矢野琢也, 小林剛, 大段秀樹.
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-29
• [Presentation] 肝移植後肝癌再発におけるNK細胞機能脆弱化のメカニズムの解明 (2016)
  • Author(s): 矢野琢也, 大平真裕, 中野亮介, 石山宏平, 井手健太郎, 田原裕之, 清水誠一, 佐伯吉弘, 坂井寛, 石田伸樹, 柳川泉一郎, 田中飛鳥, 尾上隆司, 田中友加, 大段秀樹.
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-29
• [Presentation] CD34+細胞を用いた活性化自然免疫細胞リモデリングと抗腫瘍機能解析 (2016)
  • Author(s): 田中友加, 清水誠一, 堀田龍一, 大段秀樹.
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-29
• [Presentation] Immunotherapy using donor liver NK cells for preventing severe infection after liver transplantation (2016)
  • Author(s): 石山宏平, 大平真裕, 小林剛, 井手健太郎, 田原裕之, 矢野琢也, 清水誠一, 中野亮介, 大段秀樹.
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-13
• [Presentation] 肝癌とNK細胞 (2016)
  • Author(s): 大段秀樹
  • Organizer: 第13回日本免疫治療学会研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-02-27
  • Invited
• [Presentation] Adjuvant immunotherapy using liver NK Cells enhances protective immunity against HCC recurrence and infectious complications in liver transplantation (2016)
  • Author(s): Ohdan H
  • Organizer: GAP (Global Academic Program) related Meeting Between Hiroshima University and The University of Texas MD Anderson Cancer Center
  • Place of Presentation: Hiroshima, Japan
  • Int'l Joint Research / Invited
• [Presentation] Up-regulation of anti-tumor activity on liver NK cells under the fasting condition. (2015)
  • Author(s): Tanaka Y, Ohdan H.
  • Organizer: TSS2015 14th Transplantation Science Symposium
  • Place of Presentation: Lorne, Australia
  • Year and Date: 2015-11-11
  • Int'l Joint Research
• [Presentation] 肝細胞癌切除後再発抑制に対するNK細胞免疫賦活療法の可能性 (2015)
  • Author(s): 谷峰直樹, 田中友加, 小林剛, 石山宏平, 大平真裕, 田原裕之, 黒田慎太郎, 安部智之, 岩子寛, 清水誠一, 橋本昌和, 坂井寛, 矢野琢也, 田代裕尊, 大段秀樹
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-11
• [Presentation] 肝移植術後抗HCV療法の効果に対する自然免疫関連 一塩基多型の影響解析 (2015)
  • Author(s): 清水誠一, 田中友加, 石山宏平, 尾上隆司, 井手健太郎, 大平真裕, 田原裕之, 安部智之, 谷峰直樹, 佐伯吉弘, 坂井寛, 矢野琢也, 石田伸樹, 柳川泉一郎, 佐々木由布, 小林剛, 黒田慎太郎, 田代裕尊, 大段秀樹.
  • Organizer: 第33回日本肝移植研究会
  • Place of Presentation: 神戸
  • Year and Date: 2015-05-28
• [Presentation] 絶食ストレスはHSP70 発現を介し肝臓内NK 細胞のTRAIL 依存性抗腫瘍活性を増強する (2015)
  • Author(s): 田中友加, 大段秀樹
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-04-21
• [Presentation] 肝細胞癌切除後再発予後に対するNK 細胞License の累積効果 (2015)
  • Author(s): 谷峰直樹, 田中友加, 小林剛, 田代裕尊, 大段秀樹.
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16