• CCR2およびCCR5は、いずれもT細胞Treg、単球、MDSC およびTAM に発現しています1-6
    • CCR2およびCCR5は、間質 を介した免疫抑制細胞の動員を制御します7,8
    • CCR2およびCCR5のリガンドは、それぞれ、CCモチーフ型ケモカインリガンド2(CCL2)および同5(CCL5)です3,7
  • がん細胞および間質細胞に発現するCCL2およびCCL5は、免疫抑制的なTreg、TAMおよびMDSCの細胞表面上のCCR2およびCCR5とそれぞれ相互作用することで、それらの細胞の走行と浸潤を促進します2,3,6-8,10,11



  • 腫瘍では、CCR2シグナル伝達を利用して、炎症性単球が骨髄から血液中および炎症部位へ動員され、腫瘍微小環境に浸潤します9,11,12
    • これらの単球は、細胞傷害性T細胞の増殖と機能を抑制するTAMのような、腫瘍促進的なマクロファージへと分化します9,11,12
  • CCR5は、MDSCの分化誘導をするとともに、単球を腫瘍促進的なTAMへ分化するよう刺激します7
  • 進行した固形がんの一部では、CCR2、CCR5およびそれらのリガンドの発現が上昇し、がん細胞の生存を促進している可能性が示唆されています9,13,14



  • 前臨床試験のデータでは、CCR2およびCCR5をそれぞれ、または同時に、枯渇させるもしくは阻害することで、MDSC、TAMおよびTregの腫瘍微小環境への浸潤が減少することが示唆されています10,11,15-17



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