Research for realization of cancer therapy targeted for T cell negative pathway of hepatocellular carcinoma

• Project/Area Number: 24791445
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Nara Medical University
• Principal Investigator: HOKUTO Daisuke 奈良県立医科大学, 医学部附属病院, 研究員 (70526821)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HVEM / 腫瘍免疫 / T細胞不活化経路 / 肝細胞癌 / 腫瘍内浸潤リンパ球 / 免疫治療

Research Abstract

Herpes virus entry mediator (HVEM) also known as TNFR superfamily 14 (TNFRSF14) is known to regulate immune response in immunity of infection, transplantation and tumor. However expression of HVEM in human cancer has not been well studied. This study aimed to clarify clinical importance of HVEM in human hepatocellular carcinoma.We studied HVEM expression in 150 HCC patients to explore its clinical relevance, prognostic value, and tumor infiltrating Tcells. High HVEM expression was significantly correlated with vascular invasion, PIVKA-II level, and TNM Stage.And it was inversely correlated with tumor-infiltrating CD4, CD8 and CD45RO lymphocytes and expression of perforin, granzyme B, IFN in HCC. More importantly, the HVEM status was identified as an independent prognostic factor. Conclusion: HVEM expression in HCC induces malfunction of TILs and tumor immunity. Therefore, HVEM may be a new therapeutic target for human hepatocellular carcinoma.

Research Products

• [Presentation] ヒト肝細胞癌におけるHVEM発現の臨床病理学的意義および獲得免疫機構との関連 (2012)
  • Author(s): 北東大督
  • Organizer: 日本癌治療学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ヒト肝細胞癌におけるHVEM 発現の臨床病理学的意義
  • Author(s): 北東大督, 庄 雅之, 山田高嗣, 野見武男, 山戸一郎, 赤堀宇広, 安田里司, 尾原伸作, 川口千尋, 金廣裕道, 中島祥介
  • Organizer: 第112 日本外科学会
• [Presentation] ヒト肝細胞癌におけるHVEM 発現の臨床病理学的意義および獲得免疫機構との関連
  • Author(s): 北東大督, 庄 雅之, 山田高嗣, 野見武男, 山戸一郎, 赤堀宇広, 安田里司, 尾原伸作, 川口千尋, 金廣裕道, 中島祥介
  • Organizer: 第48回 日本癌治療学会