Characterization of the tumor-immune microenvironment of lung cancer using quantitative phosphor-integrated dot staining: Toward personalized immunotherapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: INAMURA Kentaro 公益財団法人がん研究会, がん研究所 病理部, 主任研究員 (40442545)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肺がん / 腫瘍微小環境 / 免疫チェックポイント阻害薬 / 免疫療法 / 個別化医療

Outline of Final Research Achievements

Advances in genomics have markedly advanced our understanding of tumor cell properties; however, the tumor microenvironment, which encompasses complex interactions between various cell types, remains less characterized. Utilizing a cluster analysis of lung adenocarcinoma microenvironments, based on tumor-infiltrating immune cells, we uncovered four distinct subgroups. Furthermore, an additional cluster analysis of PD-L1-positive lung adenocarcinomas identified a group characterized by an elevated CD8-positive/FOXP3-positive lymphocyte ratio, correlating with a better prognosis. Our findings reaffirm the heterogeneous nature of lung adenocarcinoma, encompassing tumor-infiltrating immune cells, driver mutations, and patient characteristics. To further characterize the lung cancer immune microenvironment, it is essential to expand the sample size, encompass a wider array of immune cell types, and incorporate extensive genomic data alongside treatment response information.

Free Research Field

Tumor microenvironment

Academic Significance and Societal Importance of the Research Achievements

PD-1/PD-L1阻害薬をはじめとする免疫療法薬は、肺がん治療の有望な選択肢として注目されているが、治療効果を正確に予測することはできない。肺がんの微小環境を、免疫細胞に基づいてクラスタ解析すると、EGFR変異等の遺伝子異常や患者の喫煙習慣などと関連する特徴的な4群に層別化された。さらに、免疫チェックポイント分子であるPD-L1を発現する肺がんの中には、炎症反応の目立つ、予後が良好な1群が存在することが明らかになった。本研究成果は、肺がんの個別化治療の開発に貢献することで、肺がん患者の治療効果向上につながることが期待される。