ミエロイド細胞におけるLC3関連ファゴシトーシスは,腫瘍に対する免疫耐性を促進する
Larissa D Cunha1, Mao Yang1, Robert Carter2
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell
|September 25, 2018
まとめ
骨髄細胞におけるLC3関連ファゴサイトーシス (LAP) を損なうことは,正規のオートファギーではなく,抗腫瘍免疫を強化する. この欠陥は腫瘍関連マクロファージ (TAM) の炎症反応を誘発し,腫瘍の成長を制御する.
科学分野:
- 免疫学
- 細胞生物学
- 癌 研究
背景:
- オートファギーを標的とするのが 癌治療の目標ですが その成分には様々な役割があります
- LC3関連ファゴシトーシス (LAP) は,ファゴソームの成熟とシグナル伝達におけるオートファギータンパク質の代替機能である.
研究 の 目的:
- 腫瘍の微小環境におけるLAPの役割を,正規のオートファギと区別する.
- 骨髄細胞におけるLAPの低下が抗腫瘍免疫に影響するかどうかを判断する.
主な方法:
- 骨髄細胞における遺伝子発現を分析するために単細胞RNA配列解析 (RNA-seq) を利用した.
- 腫瘍関連マクロファージ (TAM) と抗腫瘍反応に対するLAP障害の影響を調査した.
主要な成果:
- 骨髄細胞におけるLAPの障害は,TAMによる腫瘍の成長制御を導いた.
- LAPの欠陥は,TAMにおける炎症性遺伝子発現とSTING媒介型I型インターフェロン反応を誘発した.
- LAP障害の抗腫瘍効果は,T細胞,STING,およびI型インターフェロンシグナル伝達に依存していた.
結論:
- 骨髄細胞のオートファギータンパク質は,LAPを介して免疫抑制を促進します.
- LAPをターゲットにすることで,TAMとT細胞の反応を調節することにより,抗腫瘍免疫を強化する戦略が提供されます.
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