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NF-κB c-Relは,がんにおけるT細胞免疫チェックポイントの制御に不可欠である

Yenkel Grinberg-Bleyer¹, Hyunju Oh¹, Alexis Desrichard²

¹Department of Microbiology & Immunology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.

|September 9, 2017

まとめ

調節性T細胞 (Tregs) のNF-κBc-Rel経路を阻害すると,メラノーマの成長が遅くなる. このアプローチは,Treg媒介の免疫抑制を軽減することによって,抗PD-1免疫療法を強化し,がん治療のための新しい戦略を提供します.

科学分野:

免疫学
腫瘍学
分子生物学

背景:

調節性T細胞 (Tregs) は,抗腫瘍免疫反応を抑制する上で極めて重要です.
効果的な腫瘍免疫療法には,Treg ホメオスタシスの理解が不可欠です.
カノニカル核因子 κB (NF-κB) のサブユニットであるp65とc-Relは,Tregのアイデンティティと機能の鍵である.

研究の目的:

調節性T細胞 (Treg) 機能と腫瘍免疫におけるNF-κBc-Relの特定の役割を調査する.
メラノーマの治療におけるNF-κBc-Relを阻害する治療の可能性を決定する.

主な方法:

Tregsにおけるc-Relの特定の切除によるマウスモデルを使用した.
c-Relを欠いたマウスにおけるメラノーマの成長と,Tregsにおけるp65の成長を評価した.
抗PD-1免疫療法と併用して,c-Rel機能を化学的に抑制する.

主要な成果:

NF-κB c-Relの消去は,特に活性化されたTregs (aTregs) の生成と維持を阻害した.
メラノーマの成長は,Tregsでc-Relが欠けていたマウスでは有意に減少したが,p65では減少しなかった.
c- Relの化学阻害は,aTreg媒介の免疫抑制を減らし,メラノーマの成長を遅らせました.
c- Relの抑制は,抗PD-1免疫療法の有効性を強化した.

結論:

NF-κB c-Relは,腫瘍に富んだ活性化されたTregsの機能に不可欠である.
NF-κB c-Relを阻害することは,がんの免疫療法,特に抗PD-1治療を強化するための有望な治療戦略です.

キーワード:

NF-κB について癌について免疫療法規制T細胞

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