Analysis of anti-tumor immunity in steatohepatitis-related hepatocellular carcinoma

• Project/Area Number: 19K17455
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: KITAHARA MASAAKI 金沢大学, 附属病院, 助教 (70632660)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 脂肪肝炎関連肝癌 / 樹状細胞 / 抗腫瘍免疫 / 脂肪肝炎 / 肝癌

Outline of Research at the Start

本研究では，近年増加する脂肪肝炎を背景とした肝癌患者における抗腫瘍免疫の解明を，特にそのネットワークの中心的役割を担う樹状細胞に着目し，単一免疫細胞の遺伝子発現解析というアプローチを用いて行う．宿主免疫応答の司令塔である同細胞の特徴を最小単位で明らかにすると共に，末梢血や肝内に浸潤する他の免疫細胞の発現遺伝子解析データと統合することにより，その病態解明のみならず新規免疫治療への足がかりとする．

Outline of Final Research Achievements

In this study, we analyzed the peripheral blood and hepatocellular carcinoma tissue-infiltrating immune cells of patients with steatohepatitis-related hepatocellular carcinoma to characterize the immune cells involved in liver fibrosis progression and hepatocarcinogenesis. Compared with virus-related hepatocellular carcinoma, steatohepatitis-related hepatocellular carcinoma showed significant differences in immune cell profiles, including dendritic cells, which tended to be associated with treatment response and prognosis.

Academic Significance and Societal Importance of the Research Achievements

本研究では脂肪肝から肝硬変，肝癌に至るまでの進展を一種の免疫異常として捉え，宿主免疫応答の中心を担い抗原提示細胞である樹状細胞に着目し，臨床データと統合することで本疾患に特徴的な免疫細胞の基盤情報を明らかにした．本研究の結果は，脂肪肝炎を背景とする肝癌のみならず，今後他臓器癌における免疫学的側面を研究し，新規免疫治療を確立するための重要な基盤情報になると考えている．

Research Products

• [Journal Article] Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients. (2020)
  • Author(s): T Seike, E Mizukoshi, K Yamada, H Okada, M Kitahara, T Yamashita, K Arai, T Terashima, N Iida, K Fushimi, T Yamashita, Y Sakai, M Honda, K Harada, S Kaneko.
  • Journal Title: J Gastroenterol Volume: - Issue: 7 Pages: 701-711
  • DOI: 10.1007/s00535-020-01679-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation (2020)
  • Author(s): Kitahara Masaaki、Mizukoshi Eishiro、Terashima Takeshi、Nakagawa Hidetoshi、Horii Rika、Iida Noriho、Arai Kuniaki、Yamashita Taro、Sakai Yoshio、Yamashita Tatsuya、Honda Masao、Nakamoto Yasunari、Kaneko Shuichi
  • Journal Title: Translational Oncology Volume: 13 Issue: 7 Pages: 100777-100777
  • DOI: 10.1016/j.tranon.2020.100777
  • Peer Reviewed / Open Access
• [Journal Article] A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma (2020)
  • Author(s): Tamai Toshikatsu、Mizukoshi Eishiro、Kumagai Masashi、Terashima Takeshi、Iida Noriho、Kitahara Masaaki、Shimakami Tetsuro、Kitamura Kazuya、Arai Kuniaki、Yamashita Taro、Sakai Yoshio、Yamashita Tatsuya、Honda Masao、Fushimi Kazumi、Kaneko Shuichi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 4021-4021
  • DOI: 10.1038/s41598-020-60843-4
  • Peer Reviewed / Open Access
• [Presentation] Long-term presence of tumor-specific CD8 T cells over 10 years after peptide vaccination in hepatocellular carcinoma patients (2020)
  • Author(s): HIdetoshi Nakagawa, Eishiro Mizukoshi, Kiichiro Kaji, Toshikatsu Tamai, Masaaki Kitahara, Kazumi Fushimi, Shuichi Kaneko
  • Organizer: 71th AASLD
  • Int'l Joint Research