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マクロファージを通じたCD24シグナル伝達シグレック10は,がん免疫療法の標的である
Amira A Barkal1,2,3,4, Rachel E Brewer1,2,3, Maxim Markovic1,2,3
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|August 2, 2019
まとめ
癌細胞はCD47やPD-L1のような "私を食べないで"という信号を使って 免疫の検出を回避します 研究者らは,CD24が有力な免疫チェックポイントとして働き,マクロファージのクリアランスを阻害し,卵巣がんと乳がんに対する新しい免疫療法標的を提供することを発見しました.
科学分野:
- 免疫学
- 腫瘍学
- 細胞生物学
背景:
- 卵巣がんやトリプルネガティブ乳がんは 標的治療が限られ 転移率が高く 致死性があります
- 癌細胞はCD47,PD-L1,B2Mのような"私を食べないで"という信号で マクロファージのクリアランスを回避します
- これらの信号を標的とした既存の抗体療法では,他の免疫回避メカニズムが存在することを示唆する,変化する反応を示しています.
研究 の 目的:
- 癌の免疫回避に関与する 新しい"食べないで"信号を特定するためです
- 卵巣および乳がんにおける潜在的な治療標的としてのCD24の役割を調査する.
- 腫瘍で発現するCD24とマクロファージの受容体の相互作用を研究する.
主な方法:
- 腫瘍関連マクロファージおよびがん細胞におけるCD24およびSiglec-10発現の分析
- 臨床前モデルにおけるCD24とSiglec-10の遺伝子消去
- CD24- Siglec-10の相互作用を阻害するモノクローナル抗体を用いたin vitroおよびin vivo実験.
- マクロファージのファゴシトーシス,腫瘍の成長,生存率の評価
主要な成果:
- 腫瘍発現のCD24は,卵巣がんと乳がんにおける支配的な先天性免疫チェックポイントとして特定されました.
- CD24は,シアリック酸に結合するIg型レクチン10 (Siglec-10) と腫瘍関連マクロファージに相互作用し,ファゴサイトーシスを抑制する.
- CD24- Siglec-10軸の遺伝的または抗体媒介のブロックは,腫瘍細胞のファゴシトーシスを強く強化し,腫瘍の成長を vivo で減少させた.
- 治療的なCD24阻害は,マクロファージに依存した腫瘍の減少と生存率の増加につながった.
結論:
- CD24は,複数の癌のタイプにおいて,免疫回避を促進する重要な抗ファゴサイト信号として機能する.
- CD24- Siglec-10の相互作用をターゲットにすることは,卵巣がんと乳がんに対する有望な新しい免疫療法戦略です.
- CD24阻害は免疫抵抗を克服し,これらの致命的な悪性腫瘍の治療結果を改善することができます.
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