Activation of tumor immunity by metabolic reprogramming in liver cancer microenvironment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03644
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Hino Keisuke 川崎医科大学, 医学部, 教授 (80228741)
• Co-Investigator(Kenkyū-buntansha): 仁科 惣治 川崎医科大学, 医学部, 准教授 (70550961) ; 山内 明 川崎医科大学, 医学部, 教授 (80372431)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腫瘍免疫 / がん微小環境 / 肝細胞癌 / Warburg効果 / ナノ粒子 / 2-depxy-D-glucose

Outline of Final Research Achievements

2-deoxy-D-glucose (2DG) encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (2DG-PLGA-Nps) preferentially accumulated in liver tumor in mice. 2DG-PLGA-Nps induced cytotoxic effects (oxidative stress and endoplasmic reticulum stress) and antitumor immunity through enhanced T cell trafficking induced by increased chemokine production and decreased lactate production. Consequently, 2DG-PLGA-Nps inhibited liver tumor growth in mice.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

現在がんに対する免疫療法は注目を浴びているが、本研究はがん細胞のWarburg効果を抑制する2DGが新たにがん微小環境における抗腫瘍免疫を活性化することを初めて明らかにした点で学術的意義が高い。また2DGをナノ粒子に封入することでenhanced permeability retention効果を介して腫瘍特異的なdrug delivery systemを開発し、新たな肝がん治療薬の開発に繋がる可能性を示した点で社会的意義も高い。