PD-1標的治療によるCD8 T細胞の回復はCD28に依存している

Alice O Kamphorst¹, Andreas Wieland¹, Tahseen Nasti¹

¹Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

Science (New York, N.Y.)

|March 11, 2017

まとめ

CD28/B7経路は,効果的なプログラム細胞死-1 (PD-1) 治療に不可欠です. この研究は,がんやウイルス感染症で CD8 T細胞を救うために CD28 刺激が不可欠であることを示しています.

科学分野:

免疫学
癌生物学
ウイルス学

背景:

プログラム細胞死-1 (PD-1) 療法は,がんに対するT細胞の反応を高めます.
PD-1 療法の有効性における共刺激性分子の役割は完全に理解されていません.

研究の目的:

CD28/B7共刺激経路がPD-1治療の有効性にとって必要かどうかを調査する.
PD-1 阻害中のCD8 T細胞反応におけるCD28の役割を決定する.

主な方法:

CD28の細胞内部の役割を評価するためにマウスの条件付きの遺伝子削除.
ウイルス感染と腫瘍モデルにおけるPD-1治療の有効性を評価する.
PD-1治療を受けている肺がん患者のCD8T細胞を分析した.

主要な成果:

CD28はPD-1阻害後のCD8T細胞増殖のために細胞内にある必要性があります.
腫瘍を持つマウスのPD-1治療に成功するには,B7-costimulationが不可欠です.
PD-1 治療を受けた肺がん患者の増殖するCD8 T細胞は主にCD28陽性であった.

結論:

CD28/ B7共刺激経路は,PD-1療法中のCD8 T細胞救済に不可欠である.
この経路は,がん患者のPD- 1 阻害の臨床有効性において重要な役割を果たします.

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