肺がんの進化におけるネオアンチゲン誘導免疫脱出
Rachel Rosenthal1,2,3, Elizabeth Larose Cadieux4, Roberto Salgado5,6
1Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.
Nature
|March 22, 2019
まとめ
免疫マイクロ環境は 肺がんの早期進化を形作り 様々なメカニズムを通して 免疫逃避を促します これらのプロセスを理解することは 患者の治療結果を予測し 効果的な治療法を開発するために 極めて重要です
科学分野:
- 腫瘍学
- 免疫学
- 遺伝学
背景:
- 進化する癌と免疫マイクロ環境のダイナミックな相互作用は完全に理解されていません.
- 早期の未治療非小細胞肺がん (NSCLC) は,これらの相互作用を研究するための重要なウィンドウです.
- 腫瘍に浸透するリンパ球 (TILs) は,がんの進行に影響を与える免疫微環境の重要な構成要素です.
研究 の 目的:
- 早期NSCLCにおける免疫浸透と腫瘍の進化の関係を調査する.
- 腫瘍の微小環境によって引き起こされる 免疫逃避のメカニズムを特定する
- これらの免疫回避戦略の臨床的関連性を決定する.
主な方法:
- 88人の早期NSCLC患者の258の腫瘍領域の分析
- TILの推定のためにRNAシーケンシングとヒストパトロジーを利用した.
- ネオアンチゲン表現,ヒト白血球抗原 (HLA) ステータス,遺伝子プロモーターメチル化を調べた.
主要な成果:
- 免疫浸透は,腫瘍内および腫瘍間において有意に変化した.
- 異なる免疫微環境は,異なるネオアンチゲンプレゼンテーションの欠陥と関連していました.
- 免疫回避のメカニズムには,歴史的免疫編集,コピー数減少,HLAヘテロジゴシティの減少,ネオアンチゲンの減少,およびプロモーターハイパーメチル化による表遺伝子の静止が含まれていた.
- ネオアンチゲン遺伝子のプロモーター高メチル化が表遺伝的免疫編集メカニズムとして特定された.
結論:
- 免疫マイクロ環境は初期段階のNSCLCに強い選択圧力をかけます
- 腫瘍の進化によって 免疫逃避への複数の経路が確立されています
- これらの免疫回避メカニズムは臨床的に重要であり,疾患のない生存率の低下と関連しています.
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