IL-23は腫瘍の発生と成長を促進する

John L Langowski¹, Xueqing Zhang, Lingling Wu

¹Schering-Plough BioPharma, 901 California Avenue, Palo Alto, California 94304, USA.

Nature

|May 12, 2006

まとめ

インターリューキン-23 (IL-23) は,腫瘍の炎症を促進し,細胞毒性T細胞の浸透を減らすことで免疫監視を妨げます. IL-23の除去は,抗腫瘍免疫力を高め,がんの発症から保護します.

科学分野:

腫瘍学腫瘍学
免疫学免疫学とは
炎症の研究炎症の研究

背景:

慢性炎症は,がん発生率の増加と関連しています.
腫瘍関連炎症は,免疫細胞の浸透と血管新生を含む慢性炎症とのメカニズムを共有しています.
細胞毒性T細胞によって媒介される免疫監視は,早期の悪性病変の排除に不可欠です.

研究の目的:

腫瘍関連炎症と免疫監視障害の間の分子関連性を調査する.
腫瘍の微環境と免疫細胞の浸透を調節するインタールイキン-23 (IL-23) の役割を決定する.
癌の予防と治療におけるIL-23を標的とした治療の可能性を評価する.

主な方法:

人間の腫瘍におけるIL-23およびIL-12発現の分析.
IL-23が炎症反応,マトリックスメタロプロテアゼ活性,血管新生に及ぼす影響を調査する.
IL-23調節に反応するCD8T細胞の浸透を評価する.
化学的に誘発されたおよび移植された腫瘍のマウスモデルにおけるIL-23の遺伝子消去と抗体媒介による除去を活用する.

主要な成果:

IL-23の発現は,その相対的なIL-12とは異なり,ヒト腫瘍では上昇しています.
IL-23は,炎症反応を促進し,マトリックスメタロプロテアゼ9 (MMP9) のアップレギュレーション,および血管新生を促進します.
IL-23は,細胞毒性CD8T細胞が腫瘍に浸透するのを阻害する.
IL-23の枯渇または阻害は,細胞毒性T細胞の浸透を促進し,化学的に誘発された発がんから保護します.
IL-23欠乏症またはIL-23受容体欠乏症のマウスでは,腫瘍の成長が制限されています.

結論:

IL-23は,腫瘍を誘発する炎症と適応免疫監視の失敗を結びつける重要な分子媒介体として作用する.
IL-23をターゲットにすることで,エフェクター細胞が腫瘍に浸透する障害を克服し,抗腫瘍免疫力を高めることができます.
IL-23の調節は,がんの免疫療法の有望な戦略です.

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