NKG2D受容体のRae1とH60リガンドは,腫瘍免疫を刺激する
A Diefenbach1, E R Jensen, A M Jamieson
1Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley 94720, USA.
Nature
|September 15, 2001
まとめ
腫瘍細胞にNKG2DリガンドRae1betaまたはH60を導入すると,自然キラー (NK) 細胞とCD8+T細胞による強力な拒絶が引き起こされます. この発見は,NKG2Dリガンドが新しい腫瘍ワクチンの開発に役立つ可能性を示唆しています.
科学分野:
- 免疫学 免疫学とは
- がん生物学 がん生物学
- 分子生物学は分子生物学である.
背景:
- ナチュラルキラー (NK) 細胞は抗腫瘍免疫に不可欠ですが,腫瘍細胞との相互作用は完全に理解されていません.
- 免疫細胞のNKG2D受容体は,腫瘍細胞によって発現されるリガンドを認識しますが,腫瘍の拒絶への直接的なリンクが欠けています.
- MHCクラスI分子に関連したいくつかのNKG2Dリガンドは,腫瘍細胞上位調節されているが,拒絶における役割は不明である.
研究 の 目的:
- 腫瘍細胞の拒絶におけるNKG2Dリガンドの役割を調査する.
- 腫瘍細胞にNKG2Dリンガンを発現させることで,抗腫瘍免疫反応を誘発できるかどうかを判断する.
- 癌ワクチン開発におけるNKG2Dリガンドの可能性を調査する.
主な方法:
- 様々な腫瘍細胞系におけるマウリンNKG2Dリガンド (Rae1betaまたはH60) の子宮外発現.
- 腫瘍細胞の拒絶をシンジェニックマウスで評価する.
- NK細胞とCD8+T細胞の活動を含む免疫応答の評価.
- リガンド発現性腫瘍細胞に曝露した後に腫瘍を患ったマウスを挑戦する.
主要な成果:
- Rae1betaまたはH60リガンドの子宮外発現は,シンジェニックマウスの腫瘍細胞の強力な拒絶につながった.
- 腫瘍の拒絶はNK細胞とCD8+T細胞の両方によって媒介された.
- リンガンを発現する腫瘍細胞は,細胞毒性T細胞の有意なプライミングを誘導し,NK細胞の感受性を in vivoで引き起こす.
- リガンド発現する腫瘍細胞に曝露されたマウスは,その後の腫瘍への挑戦に対して特定の免疫を発達させた.
結論:
- 腫瘍細胞にNKG2DリガンドRae1betaまたはH60が発現すると,強力な抗腫瘍免疫が生じます.
- NKG2Dリガンドは,NKとCD8+T細胞によって媒介される腫瘍細胞の拒絶に重要な役割を果たします.
- これらの発見は,効果的な腫瘍ワクチンの設計におけるNKG2Dリガンドの潜在的な応用を支持する.
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