腫瘍MHCクラスI制限抗原と腸内細菌菌との交叉反応性

Aurélie Fluckiger^1,2, Romain Daillère^1,2,3, Mohamed Sassi⁴

¹Gustave Roussy Cancer Campus (GRCC), Villejuif, France.

Science (New York, N.Y.)

|August 22, 2020

まとめ

腸内細菌は免疫細胞を訓練して癌と戦うことができます特定の細菌のタンパク質 (TMP) が抗腫瘍反応を誘発し,マウスのがん免疫療法を改善し,患者の治療成功と相関していることが判明しました.

科学分野:

免疫学
微生物学
腫瘍学

背景:

腸内微生物群は,腫瘍抗原と交互反応するT細胞を誘発する可能性があります.
癌の免疫療法を強化するために微生物成分を活用できます

研究の目的:

微生物のエピトープが抗腫瘍T細胞反応を誘発するかどうかを調査する.
がん免疫療法における特定の細菌のタンパク質の役割を決定する.

主な方法:

Enterococcus hirae プロファージの尾長測定テープタンパク質 (TMP) のMHCクラスI結合エピトープを特定した.
免疫療法を受けているマウスにTMPエピトープを発現する人工細菌株を投与した.
マウスのTMP特異性CD8+T細胞反応を分析した.
がん患者における免疫療法のアウトカムと相関する腸内球菌のプロファージ存在とTMPクロス反応性抗原発現.

主要な成果:

プロファージを宿すマウスは,免疫療法でTMP特異的なCD8+T細胞反応を示した.
TMPエピトープを発現する改造されたバクテリアはマウスの免疫療法の成果を向上させた.
腎臓および肺がん患者におけるPD- 1 阻害療法からの長期的利益と相関するエントロコックスのプロファージの存在とTMPクロス反応性腫瘍抗原.
メラノーマ患者で微生物ペプチドと交互反応するT細胞クローンが検出されました.

結論:

TMPのような共生由来の微生物エピトープは,抗腫瘍CD8+T細胞反応を誘発する.
微生物のエピトープを発現させるための細菌の設計は,がんの免疫療法を改善することができます.
特定の微生物抗原の存在と腫瘍抗原との交叉反応は,免疫療法反応を予測するバイオマーカーである.

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