2021 Fiscal Year Final Research Report

Search for biomarkers on immunotherapy for metastatic renal cancer by using circulating tumor cells and repertoire analysis

Research Project

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Project/Area Number	19K09739
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56030:Urology-related
Research Institution	Juntendo University
Principal Investigator	Nagata Masayoshi 順天堂大学, 医学部, 准教授 (00323668)
Co-Investigator(Kenkyū-buntansha)	長屋直哉順天堂大学, 医学部, 助教 (10795024) 堀江重郎順天堂大学, 大学院医学研究科, 教授 (40190243)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	腎細胞がん / 免疫チェックポイント阻害薬 / 血中循環腫瘍細胞 / レパトア解析 / 抗CTLA-4抗体 / 抗PD-1抗体
Outline of Final Research Achievements	Circulating tumor cells (CTC) were collected from patients with immune checkpoint inhibitor therapy (IO) for advanced renal cell carcinoma and analyzed for expression of related molecules. In addition, as a patient-side immunological analysis, comprehensive analyses are performed by repertoire analysis from peripheral blood, and biomarkers such as effect prediction and serious immune-related adverse events(irAE) predictors are searched. Expression of related molecules such as PD-L1 and EGFR could be detected by CTC from patients before IO treatment, but the efficacy was not predicted during the current observation period. Of the 6 analyzable patients who underwent IO combination therapy, 3 patients who used high-dose steroid due to severe irAE and 3 patients who did not use it are currently undergoing statistical analysis from peripheral blood B cell / T cell repertoire analysis data.
Free Research Field	進行腎がんへの薬物治療
Academic Significance and Societal Importance of the Research Achievements	今までの研究は、がん細胞における分子異常や遺伝子異常から抗がん剤の効果を予測・評価する研究が主体であった。免疫治療の有効性や免疫関連有害事象に関与するのは、がん側の要素に加えて、患者側の免疫環境も重要である。本研究の特徴は、2方向のアプローチで行なった。一つは、がん側の遺伝子変異や分子発現解析を末梢血liquid biopsyによって行ない、もう一方は、患者宿主免疫機能の側面からTCR/BCRレパトア解析を用いた。それぞれの解析手法も独自の手法を用いた。dataは複雑であるが、免疫側からのアプローチによって有効性や有害事象を予測しうるバイオマーカー開発は現在の免疫治療時代に有用となりうる。