NKG2Aブロックは,がんワクチンによって誘発されたCD8T細胞の免疫を強化する

Nadine van Montfoort¹, Linda Borst¹, Michael J Korrer²

¹Department of Medical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, the Netherlands.

Cell

|December 4, 2018

まとめ

NKG2A (抑制受容体) を阻害すると,CD8T細胞を活性化することで,治療的ながんワクチンを強化する. このアプローチは治療が難しい腫瘍でも患者の反応を改善する見込みです

科学分野:

免疫学
癌研究
T細胞生物学

背景:

腫瘍に浸透するCD8T細胞は,しばしば抑制受容体NKG2Aを発現する.
NKG2Aの発現は,免疫反応性腫瘍およびがん後のワクチン接種で一般的です.
NKG2Aは,一般的な免疫チェックポイント阻害剤とは独立したCD103を共発する異なるCD8T細胞サブセットを識別する.

研究の目的:

NKG2Aをがんワクチンに対する潜在的適応抵抗メカニズムとして調査する.
臨床前がんモデルにおけるNKG2A/ Qa-1b軸の阻害による治療の可能性を評価する.

主な方法:

NKG2A+ CD8 T細胞を特徴づけるために高次元クラスター解析を用いた.
4つのマウス腫瘍モデルでNKG2Aの抗体阻害とそのリガンドQa-1b (HLA- Eオートログ) のノックアウトを施した.
NKG2A/ Qa-1b軸の障害が治療的がんワクチンの有効性に与える影響を評価した.

主要な成果:

NKG2A/ Qa- 1b軸の障害は,治療用がんワクチンの有効性を著しく強化した.
強化されたワクチンの反応は,PD-1耐性マウスモデルでも観察された.
NKG2A阻害療法では,NK細胞ではなくCD8T細胞が作用した.

結論:

NKG2Aは,がんワクチンの有効性を制限する適応性耐性メカニズムとして作用します.
NKG2A/ Qa- 1b軸を遮断することで,ワクチン耐性を克服できます.
NKG2Aを阻害する抗体は,がんワクチンの臨床反応を改善するための有望な戦略です.

キーワード:

CD8 T細胞 HLA-E IFN-γ NKG2A QA-1 について獲得した抵抗性がんワクチン免疫チェックポイントマウス腫瘍モデル自然殺虫細胞

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