MYCは,CD47とPD-L1を通して抗腫瘍免疫反応を調節する

Stephanie C Casey¹, Ling Tong¹, Yulin Li¹

¹Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Science (New York, N.Y.)

|March 12, 2016

まとめ

MYC腫瘍遺伝子は免疫チェックポイントCD47とPD-L1を制御することで癌を誘発する. MYCを抑制すると,これらのチェックポイントが減り,抗腫瘍免疫が強化され,がんの成長が妨げられます.

科学分野:

腫瘍学
免疫学
分子生物学

背景:

MYC腫瘍遺伝子はヒトのがんでは頻繁に過剰発現しています.
MYCは細胞の成長と増殖に関与する転写因子です.
CD47やPD-L1のような免疫チェックポイントは,腫瘍の免疫回避に重要な役割を果たします.

研究の目的:

免疫チェックポイントタンパク質CD47とPD-L1の調節におけるMYCの役割を調査する.
MYCがCD47とPD-L1の発現に直接影響するかどうかを判断する.
MYC媒介の免疫チェックポイントの反腫瘍免疫反応への影響を明らかにする.

主な方法:

MYC抑制はマウス腫瘍モデルとヒト腫瘍細胞系で誘発された.
CD47とPD- L1のmRNAとタンパク質レベルの定量分析
MYCが遺伝子プロモーターに結合することを評価するクロマチンの免疫プレシピテーションアッセイ
MYCの不活性化後の抗腫瘍免疫反応の評価

主要な成果:

MYCを抑制すると,mRNAとタンパク質レベルでのCD47とPD- L1の両方の発現が低下しました.
MYCはCd47およびPd-l1遺伝子のプロモーター領域に直接結合することが示された.
MYCの不活性化により,抗腫瘍免疫反応が強化された.
MYCが不活性化した腫瘍におけるCD47またはPD- L1の発現は,強化された免疫反応を無効化し,腫瘍の成長を促した.

結論:

MYCは,免疫チェックポイントタンパク質CD47とPD- L1の発現を調節することによって,腫瘍形成に重要な役割を果たします.
これらの免疫チェックポイントのMYCの調節は,免疫回避と腫瘍の進行に不可欠です.
MYCを標的とした治療は,抗腫瘍免疫を高めるための治療戦略である.

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