IDO1(Indoleamine 2,3-dioxygenase-1)は、トリプトファンをキヌレニンに代謝し、それによりT細胞の増殖が抑制され、制御性T細胞(Treg)の分化を誘導します。IDO1の阻害により、T細胞の機能が回復し、腫瘍微小環境へのTregの集積が減少する可能性があります。


  • IDO1は抗原提示細胞(APC)で発現する酵素です1,2
  • IDO1の活性化には、補因子の動的な結合が必要です3,4
    • IDO1は、細胞の生存に必須のアミノ酸であるトリプトファンを代謝し、免疫抑制的な作用をもつ代謝産物であるキヌレニン等に変換します1,5
    • 通常、キヌレニンは、T細胞の機能を抑制して過剰な免疫反応を防ぐ、拮抗的なはたらきをしています6,7



  • 腫瘍では、がん細胞およびAPCの両者でIDO1の発現が増加するようにその環境が変化しており、免疫抑制のプロセスが乗っ取られています1,8-10
    • IDO1の発現上昇によりトリプトファンが欠乏し、キヌレニン濃度が上昇し、これによりT細胞の増殖が抑制され、Tregの分化が誘導され、がん細胞の生存が助長されます11-14
    • IDO1発現の増加は、多くの固形がんおよび造血器腫瘍における予後不良または転帰不良と関連付けられます14-19



  • 前臨床試験では、IDO1の阻害により免疫抑制的なTregの数が減少し、細胞傷害性T細胞の機能が回復することが示されています14,20
    • さらに、IDO1阻害と免疫チェックポイント経路の阻害を組み合わせると、相乗的に、T細胞の増殖が亢進し、Tregの集積が減少する可能性があります13,21,22





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