Elucidation of tumor immune regulatory mechanism by histone methyltransferase G9a and its application as a therapeutic target

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16301
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nagoya University
• Principal Investigator: Kato Shinichiro 名古屋大学, 医学系研究科, 特任助教 (40751417)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: エピジェネティクス

Outline of Final Research Achievements

Immune Checkpoint Blockade (ICB) has revolutionized cancer therapy with its extraordinal therapeutic effects, but the response rate is limited except for some patients with certain cancer harboring high mutation burdens. Here, we focused on an oncogene called histone methyltransferase G9a, which we have discovered in cutaneous melanoma, and investigated the role of G9a not only in the malignant transformation but also in the anti-tumor immune system in tumors to comprehensively figure out the mechanism of tumor malignant development via immune evasion. We have provided a mechanistic insight into tumorigenesis and tumor immune regulation by G9a and its potential as a therapeutic target in combination with or without ICB in melanoma and other tumors.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

現在、さまざまながん種においてICB単剤もしくは多剤併用による臨床試験が進められていることから、ICBを代表とするがん免疫療法に対する期待の高さが伺える。ところが、実際にその恩恵は一部のがん種、がん患者に限定されており、治療抵抗性・耐性化の分子基盤の解明が社会的にも強く求められている。本研究成果により、がん細胞のエピゲノムランドスケープが腫瘍免疫環境に影響を及ぼすという学術的新規性に加えて、特定のがん細胞における免疫回避およびICB抵抗性がG9aにより制御されることが明らかにされたことから、治療抵抗性の克服に向けた重要な知見が提供された。