Identification of Treatment-Related Factors Using Multi-Region Analysis Before and After Cancer Immunotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15576
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kamatani Takashi 東京医科歯科大学, M&Dデータ科学センター, 講師 (90645764)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: マルチオミックス / がん免疫 / 免疫チェックポイント阻害薬

Outline of Final Research Achievements

This study identified factors related to the effectiveness of cancer immunotherapy through multi-region sequencing analysis conducted before and after treatment. Specifically, we examined: (1) the evolution of tumor tissue pre- and post-treatment, (2) differences in treatment effects across different organs within the same patient and their pathological and genetic disparities, and (3) the development of resistance to immune checkpoint inhibitors (ICIs) and related tumor characteristics. We identified subclones associated with treatment effectiveness and elucidated the biological and immunological features of “malignant subclones” involved in cancer progression. Additionally, we validated the malignancy of these subclones using public databases and assessed the impact of selective pressures by analyzing mutation pathogenicity and subclone growth processes.

Free Research Field

バイオインフォマティクス

Academic Significance and Societal Importance of the Research Achievements

本研究は、がん免疫療法における腫瘍進化の理解を深め、治療効果に影響を与える因子や耐性機構の解明に貢献しました。学術的には、がん進行と治療効果に関連する新たな生物学的・遺伝学的知見を発見し、今後の個別化医療の発展に寄与すると考えます。社会的には、治療効果を向上させるための新たな戦略や、治療抵抗性がんの対策に向けた基礎データとして利用でき、がん治療の効果改善に寄与すると考えます。