エフェクターT細胞は,卵巣がんにおけるストロマ媒介の化学抵抗を抑制する

Weimin Wang¹, Ilona Kryczek², Lubomír Dostál³

¹Department of Obstetrics and Gynecology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.

Cell

|May 3, 2016

まとめ

卵巣がんでは細胞内のプラチナを減少させることで化学療法への耐性を引き起こしますエフェクタ T 細胞は繊維細胞の代謝を変化させることでこの抵抗を克服し新しい治療戦略を提案します

科学分野:

腫瘍学
免疫学
細胞生物学

背景:

腫瘍の微小環境は,エフェクターT細胞と線維芽細胞で構成されています.
化学抵抗に影響する細胞相互作用のメカニズムは不明である.

研究の目的:

卵巣がんにおけるフィブロブラストとT細胞の化学抵抗性への影響を調査する.
プラチナベースの化学療法に対する細胞相互作用の役割を明らかにする.

主な方法:

卵巣がん細胞におけるプラチナの蓄積を評価した.
線維細胞によって放出されるグルタチオンの役割を分析した.
線維細胞の代謝に対するCD8 ((+)) T細胞の影響を研究した.
関連するシグナル伝達経路 (JAK/STAT1) と分子 (IFNγ) を調査した.

主要な成果:

卵巣がん細胞のプラチナ核の蓄積を減少させ,化学抵抗を引き起こす.
繊維細胞に由来するグルタチオンとシステインがこの抵抗を媒介する.
CD8 ((+)) T細胞は,IFNγシグナル伝達を通じて,繊維細胞のグルタチオンとシスティンの代謝を調節することによって,化学抵抗を逆転させます.
ストロマル・フィブロブラストは患者の生存率の低下と相関し,CD8 ((+)) T細胞は生存率の改善と相関する.

結論:

エフェクターT細胞は,卵巣がんにおけるストロマ線維細胞媒介の化学抵抗に対抗する.
化学療法と免疫療法の相互作用をターゲットにすることで治療への希望が生まれます

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