Exploration of fatty acid metabolism that can activate immune checkpoint pathway in breast cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16254
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Kawashima Masahiro 京都大学, 医学研究科, 助教 (80766676)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 脂肪酸 / 免疫チェックポイント / 乳癌 / 温度 / 代謝 / 低酸素 / ストレス応答 / 放射線治療

Outline of Final Research Achievements

In this study, we explored the molecular mechanisms underlying the strong correlation between fatty acid metabolism and tumour immune activity in breast cancer tissue, as revealed by the analysis of clinical breast cancer samples. The results showed that the expression of a fatty acid binding protein, FABP7 in breast cancer cells 1) regulates the expression of PD-L1, a regulatory molecule of the immune checkpoint, 2) strongly determines the ability to proliferate from a single cell, 3) is involved in resistance to oxidative stress such as irradiation and hypoxia, 4) is involved in cellular heat production and temperature regulation. These results suggested that FABP7 and tumour immune activity do not simply correlate one-to-one, and that FABP7 regulates tumour immunity by modifying multiple cellular functions especially stress response and thermal metabolism.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

FABP7が乳がん細胞の免疫反応、増殖能、幹細胞性、ストレス耐性、細胞温度など様々な機能を直接的あるいは間接的に制御していることが示唆された。特に、FABP7によるPD-L1の発現制御や温度制御との関連はこれまでに既報がない重要な発見であった。本研究で得られた知見を、今後乳がんの免疫療法の進歩にどのように繋げていくかについてはさらなる注意深い検証が必要であるが、乳がんの生物学に「温度と免疫と脂肪酸」という全く新しい概念を提示できたことは本研究の貴重な成果であると考えられた。