免疫チェックポイント阻害薬の治療効果と宿主HLA及び腫瘍免疫微小環境の統合解析

免疫检查点抑制剂、宿主HLA、肿瘤免疫微环境的治疗效果综合分析

• 批准号: 21K09359
• 负责人: 近藤 恒徳
• 金额: $ 2.66万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K09359/
• 关键词: 腎癌; HLA; 腫瘍微小環境; 免疫細胞; 網羅的遺伝子発現解析

腎細胞がんの全身療法は、分子標的薬に続いて免疫チェックポイント阻害剤 (ICI)が導入され、以前と比べて治療効果は向上したものの、その効果を示す患者は限定的である。そのため、治療効果を予測するバイオマーカーや現行治療に反応しない症例に対する新規治療標的の探索が急務となっている。本研究では、ICIの奏功データと紐づいた腎細胞がんの臨床検体に対して、末梢血単核球を用いたHLAタイピング、腫瘍浸潤免疫細胞のフローサイトメトリー解析及び腫瘍微小環境に関する網羅的遺伝子発現解析を行い、それらのデータとICIの効果との関連性について統合的に解析することを目的とする。これらの研究成果は、ICIの効果予測マーカーと腎細胞がんの新規治療標的の探索へ展開することが期待される。本研究全体として30 - 40症例のHLAタイピング、腫瘍浸潤免疫細胞のフローサイトメトリー解析及び網羅的遺伝子発現解析を横並びで行う予定であるが、2021年度は30症例の末梢血単核球からHLA解析用のDNAを抽出し保存した。2022年度はさらに10症例を追加し、目標の40症例のDNA抽出を終了した。またこれらのうち20症例を次世代シーケンサーを用いてHLAタイピングを行いデータを得た。またこれらの症例のうち23症例は腎細胞がんの原発巣の外科的切除を行なっており、外科切除検体から抽出した腫瘍浸潤免疫細胞を単一細胞化し細胞保存液で-80℃に保存しているが、これらのフローサイトメトリー解析を終了しデータを得た。

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