ペプチドグリカンの改造は,チェックポイント阻害剤のがん免疫療法を促進します

Matthew E Griffin^1,2,3,2,1, Juliel Espinosa^1,2, Jessica L Becker^1,2

¹Departments of Immunology and Microbiology and Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|August 27, 2021

まとめ

腸内細菌は免疫活性分子を生成することで癌の免疫療法を強化しますこれは,特定の細菌酵素とムロペプチドが,新しいがん治療補助剤として開発される可能性があることを示唆しています.

科学分野:

微生物学
免疫学
腫瘍学

背景:

腸内微生物の構成は,がん免疫療法の有効性に影響します.
腸内細菌と免疫療法の反応を結びつける分子メカニズムは完全に理解されていません.

研究の目的:

ガンに対する免疫療法の強化におけるバクテリア属"Enterococcus"の役割を調査する.
免疫療法に対する宿主反応に影響を与える分子機構を特定する.

主な方法:

チェックポイント阻害剤の免疫療法に対するEnterococcusの影響を評価するためにマウス腫瘍モデルを使用した.
SagA酵素の発現と機能,免疫活性ムロペプチドの生成におけるその役割について調査した.
NOD2センサーのSagaA活性と免疫療法応答の必要性を検討した.

主要な成果:

* エントロコッカス * 種は,マウスモデルでのチェックポイント阻害剤免疫療法を改善することが判明しました.
細菌の酵素SagA (NlpC/p60ペプチドグリカンヒドローラゼ) は,免疫活性ムロペプチドを生成する.
*E. faecalis* での SagAの発現は,NOD2センサに依存して,免疫療法の反応を強めた.
SagA活性を含む合成のプロバイオティクスは,抗PD- L1の有効性を高めました.

結論:

SagAのような酵素によって媒介される細菌のペプチドグリカン改造活動は,癌の免疫療法を強化する.
バクテリアによって生成される免疫活性ムロペプチドは,免疫療法の結果を改善する補助剤として機能する.
バクテリアの酵素やムロペプチドをターゲットにすることで次世代のがん治療薬の戦略が生まれます

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