腫瘍血管の正常化と免疫刺激の再プログラミングの相互調節
Lin Tian1,2,3, Amit Goldstein1,2,4, Hai Wang1,2,4
1Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Nature
|April 4, 2017
まとめ
1型ヘルパー (TH1) 細胞は,腫瘍の血管を正常化し,治療の有効性を改善するために不可欠です. この発見は,TH1細胞が腫瘍血管系と免疫反応を調節する新たな役割を明らかにしています.
科学分野:
- 免疫学
- 腫瘍学
- 血管生物学
背景:
- 抗血管新生療法によって 逆説的に腫瘍の転移が増加します
- 血管の正常化は, perfusion の改善と hypoxia の減少によって特徴付けられ,このパラドックスを解決することができます.
- 容器の正常化に関する規制メカニズムは,まだ十分に理解されていません.
研究 の 目的:
- 腫瘍血管の正常化におけるTヘルパー1 (TH1) 細胞の役割を調査する.
- Tリンパ球の活動と血管の正常化との関係を調べる
- TH1細胞が腫瘍低酸素症を軽減できるかどうかを判断する.
主な方法:
- 腫瘍における遺伝子発現のバイオ情報分析
- 血管正常化またはTリンパ球の欠陥を持つマウスモデルを使用した.
- 血管の正常に CD4+ Tリンパ球の減少と活性化 (免疫チェックポイントブロックによる) の影響を調査した.
- 患者から派生した異種移植モデルへの採用TH1細胞移植.
主要な成果:
- Tリンパ球の浸透と活動と相関する血管正常化の遺伝子発現シグネチャー.
- CD4+Tリンパ球の枯渇は血管の正常化を阻害し,相互の調節ループを示しています.
- 免疫チェックポイントによるCD4+Tリンパ球活性化による血管正常化.
- 血管の正常化に重要な役割を果たすインターフェロン-γを分泌するTH1細胞が特定されました.
- 免疫不全マウスで培った患者由来異種移植腫瘍におけるTH1移植は低酸素症を減少させた.
結論:
- 1型ヘルパー (TH1) 細胞は,腫瘍血管の正常化において,これまで認識されていない重要な役割を果たします.
- TH1細胞は,腫瘍血管と免疫系との間の相互制御ループの不可欠な部分です.
- TH1細胞は,免疫チェックポイント阻害および抗血管新生治療のバイオマーカーおよび治療効果の決定因子として機能する.
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