Analysis of Predictive Biomarkers for Immune Checkpoint Inhibitors in Lung Adenocarcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10691
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Juntendo University
• Principal Investigator: Takamochi Kazuya 順天堂大学, 医学部, 准教授 (30397369)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肺腺癌 / 免疫治療 / 免疫チェックポイント阻害薬 / バイオマーカー

Outline of Final Research Achievements

Programmed death 1 (PD-1), and its associated ligand (PD-L1) checkpoint blockade immunotherapy caused a new paradigm shift in treatment for patients with non-small cell lung cancer (NSCLC). Appropriate patient selection is critically important. To identify predictive biomarkers immune checkpoint inhibitors, we comprehensively analyzed previously reported predictive biomarkers such as smoking status, driver oncogene alterations, PD-L1 expression, MSI and tumor immune microenvironment, and clarified the reciprocal relationship among them. We showed that MSI is a rare event in lung adenocarcinoma. MSI cannot be used as a biomarker to predict the treatment effect of immune checkpoint inhibitors for lung adenocarcinoma. NSCLCs can be divisible into immunoreactive and non-immunoreactive tumors. The prognostic value differs according to the immunomodulatory target and driver oncogene status.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

肺腺癌における腫瘍局所免疫状態を包括的に解析することによって、喫煙歴、ドライバー遺伝子変異の有無、肺腺癌の組織亜型、組織学的浸潤の程度などによって、免疫関連分子の発現状態が異なることが明らかになった。本研究の成果は今後、日常臨床で有用な免疫チェックポイント阻害薬の効果予測バイオマーカーを絞り込んでいく上で、貴重な基礎データとなった。