Elucidation of molecular mechanism of the regulation of PD-L1 expression by histone methylation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K14994
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: National Hospital Organization, Kyushu Medical Center (Clinical Institute) (2018-2019); Kyushu University (2017)
• Principal Investigator: Toyokawa Gouji 独立行政法人国立病院機構九州医療センター(臨床研究センター), その他部局等, 呼吸器外科医師 (30627261)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: PD-L1 / EZH2 / 肺癌

Outline of Final Research Achievements

A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than those without it. A logistic regression analysis with backward elimination revealed that PD-L1 positivity was independently associated with the EZH2 expression. This result was published in 2019 (Annals of Thoracic Surgery). This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.
The PD-L1 expression at the mRNA level was not significantly decreased by the siRNA-mediated knockdown of EZH2 in comparison to siRNA normal control in the cellular level; therefore, the protein stability and subcellular localization of PD-L1 by EZH2 should be investigated in future studies.

Free Research Field

胸部腫瘍学

Academic Significance and Societal Importance of the Research Achievements

PD-L1とEZH2の関連についての報告はなく、本研究が世界初の報告である。免疫チェックポイント阻害剤の標的であり、かつ効果予測因子でもあるPD-L1と、代表的なヒストンメチル化酵素であるEZH2との関連を示した点で、非常に意義があるものと考える。本知見はニボルマブやアテゾリズマブなどの免疫チェックポイント阻害剤へのEZH2阻害剤の上乗せ効果の可能性を示唆するものである。