通过表达纤维细胞激活蛋白-alpha的 stromal 细胞抑制抗瘤免疫力
Matthew Kraman1, Paul J Bambrough, James N Arnold
1Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.
Science (New York, N.Y.)
|November 6, 2010
概括
纤维细胞激活蛋白-α (FAP) 表达细胞抑制抗瘤免疫力. 在小鼠模型中耗尽这些细胞导致瘤亡,并允许免疫控制,突出显示它们在免疫抑制中的关键作用.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 瘤微环境 (TME) 包括各种影响瘤进展和免疫逃避的细胞.
- 纤维细胞激活蛋白-α (FAP) 是一种标记物,在人类癌症中由特定的树皮细胞群体表达.
- 这种FAP表达细胞群与TME内的免疫抑制有关.
研究的目的:
- 为了研究FAP表达细胞在瘤微环境中的功能作用.
- 为了确定是否消去FAP表达细胞可以恢复抗瘤免疫力.
- 阐明FAP表达细胞对免疫抑制有所贡献的机制.
主要方法:
- 创建了一个转基因小鼠模型,允许对FAP表达细胞进行特定的切除.
- 在已建立的易斯肺癌和胰腺管道腺癌模型中,FAP表达细胞的枯竭.
- 分析瘤细胞和树皮细胞活力,瘤生长和免疫反应,包括干扰素-γ和瘤亡因子-α的作用.
主要成果:
- 在易斯肺癌中,FAP表达细胞 (包括~2%的瘤细胞) 的枯竭导致了癌症和树皮细胞的快速缺氧亡.
- 这种亡是由干扰素-γ和瘤亡因子-α介导的.
- 在胰腺管腺癌模型中,切除FAP表达细胞允许有效的免疫控制瘤生长.
结论:
- 表达FAP的细胞是瘤微环境的一个关键的,非冗余的组成部分.
- 这些细胞在抑制抗瘤免疫反应方面发挥着重要作用.
- 向FAP表达细胞代表了一种潜在的治疗策略,以克服免疫抑制并提高癌症治疗的疗效.
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