Establishment of efficacy prediction model and clinical application of novel epigenetic modifiers

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto University
• Principal Investigator: Nishikori Momoko 京都大学, 医学研究科, 教授 (60378635)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 悪性リンパ腫 / EZH2

Outline of Final Research Achievements

Using B-cell lymphoma lines, we comprehensively analyzed the gene expression changes induced by EZH2 inhibitors and found that EZH2 inhibitors induce the expression of a group of characteristic humoral factors related to the reactivity of NK cells and T cells. They have also been shown to have the effect of altering the tumor microenvironment of B-cell lymphoma to a certain pattern similar to that of Hodgkin lymphoma. A significant correlation was observed between the genes induced by EZH2 inhibitor treatment in B-cell lymphoma and the genes reported to be highly expressed in H/RS cells of Hodgkin lymphoma. Comparison with the gene sets that are altered by epigenetic modifier genes expressed in H/RS cells have suggested that differences in epigenome modification play a role in the development of different lymphoma disease subtypes.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

EZH2阻害薬は一部の悪性リンパ腫で承認されている新規のエピゲノム修飾薬であるが、その作用機序には不明な部分も多い。そのため本研究では、EZH2阻害薬の作用機序を解明し、薬理作用に基づいた最適な使用法を見出すことを目的とした。B細胞リンパ腫株を用いて、EZH2阻害薬によって生じる遺伝子発現変化を網羅的に解析したところ、EZH2阻害薬はNK細胞やT細胞の反応性を高める特徴的な液性因子の一群の発現を誘導し、リンパ腫の腫瘍微小環境を変化させる作用を持つことが示された。本研究より、本薬剤は免疫療法との併用により治療効果が高まる可能性が示唆された。