New classification of hepatocellular carcinoma by single cell analysis of immunome

• Project/Area Number: 16K15425
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: Mizukoshi Eishiro 金沢大学, 医学系, 准教授 (90345611)
• Research Collaborator: KISHI HIROYUKI ; HONDA MASAO ; YAMASHITA TARO ; HASHIMOTO SHINICHI
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細胞傷害性Ｔ細胞 / ヘルパーＴ細胞 / 免疫治療 / 免疫応答 / Ｔ細胞レセプター / 免疫細胞プロファイル / 制御性Ｔ細胞 / 抗腫瘍免疫 / immunome / 免疫療法 / シングルセル解析 / ペプチドワクチン / 肝細胞癌 / シングルセル / 癌 / 癌微小環境

Outline of Final Research Achievements

In this study, we identified that the type and expression levels of immune molecules expressed in tumor infiltrating immune cells are different in each hepatocellular carcinoma (HCC) patient. We also identified that the differences are deeply associated with the etiology of HCC and the expression levels of many immune molecules in non-alcoholic steatohepatitis (NASH)-related HCC patients are lower than those in hepatitis B or C-related HCC patients. In addition, immune cell profiles are also different in the 3 groups. The frequency of tumor-associated antigen-specific T cells is lower in NASH-related HCC patients compared with that of other 2 groups and it is correlated with the specific immune cell profiles.

Research Products

• [Journal Article] Association Between High-Avidity T-Cell Receptors, Induced by α-Fetoprotein-Derived Peptides, and Anti-Tumor Effects in Patients With Hepatocellular Carcinoma (2017)
  • Author(s): Nakagawa H, Mizukoshi E, Kobayashi E, Tamai T, Hamana H, Ozawa T, Kishi H, Kitahara M, Yamashita T, Arai K, Terashima T, Iida N, Fushimi K, Muraguchi A, Kaneko S
  • Journal Title: Gastroenterology. Volume: 152 Pages: 1395-1406
  • DOI: 10.1053/j.gastro.2017.02.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cellular immune responses for squamous cell carcinoma antigen recognized by T cells 3 in patients with hepatocellular carcinoma. (2017)
  • Author(s): Kaji K, Mizukoshi E, Yamashita T, Arai K, Sunagozaka H, Fushimi K, Nakagawa H, Yamada K, Terashima T, Kitahara M, Kaneko S.
  • Journal Title: PLoS One Volume: 12
  • DOI: 10.1371/journal.pone.0170291
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma. (2016)
  • Author(s): Mizukoshi E, Yamashita T, Arai K, Terashima T, Kitahara M, Nakagawa H, Iida N, Fushimi K, Kaneko S.
  • Journal Title: Cancer Immunol Immunother Volume: 65 Pages: 715-25
  • DOI: 10.1007/s00262-016-1837-2
  • NAID: 120005774910
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Immunotherapy for hepatocellular carcinoma (2017)
  • Author(s): 水腰英四郎、金子周一
  • Organizer: The Asian Pacific Association for the Study of the Liver Single Topic Conference
  • Place of Presentation: ホテルオークラJRハウステンボス（佐世保市）
  • Year and Date: 2017-04-10
  • Int'l Joint Research / Invited