Characterization of the tumor-immune microenvironment of lung cancer using quantitative phosphor-integrated dot staining: Toward personalized immunotherapy
| Project/Area Number |
19K07426
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Japanese Foundation for Cancer Research |
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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)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| 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 / 微小環境 / 免疫療法薬 / バイオマーカー |
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| Outline of Research at the Start |
PD-1/PD-L1阻害薬などの免疫療法薬が有望な肺がん治療薬として台頭してきたが、治療感受性肺がんを正確に予測することは出来ず、治療抵抗性の肺がんも多い。本研究では、蛍光ナノイメージング法を活用して、PD-1/PD-L1阻害薬が効く肺がんと効かない肺がんの免疫微小環境を詳細に調べる。治療感受性バイオマーカーおよび新規免疫療法ターゲットの同定を目指した本研究の成果は、個別化免疫療法の推進に貢献することが期待される。
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| 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.
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| 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。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.2022
Author(s)
Kunieda J, Yamashita K, Togashi Y, Baba S, Sakata S, Inamura K, Ae K, Matsumoto S, Machinami R, Kitagawa M, Takeuchi K.
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Journal Title
Cancer Science
Volume: 113
Issue: 3
Pages: 1078-1089
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Insulinoma-associated protein 1 (INSM1) is a better marker for the diagnosis and prognosis estimation of small cell lung carcinoma than neuroendocrine phenotype markers such as chromogranin A, synaptophysin and CD56.2020
Author(s)
Sakakibara R, Kobayashi M, Takahashi N, Inamura K, Ninomiya H, Wakejima R, Kitazono S, Yanagitani N, Horiike A, Ichinose J, Matsuura Y, Nakao M, Mun M, Nishio M, Okumura S, Motoi N, Ito T, Miyazaki Y, Inase N and Ishikawa Y.
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Journal Title
Am J Surg Pathol
Volume: -
Issue: 6
Pages: 757-764
DOI
Related Report
Peer Reviewed
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