瘤相关巨细胞的PD-1表达抑制了细胞和瘤免疫

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Sydney R Gordon^1,2,3,4,5, Roy L Maute^1,3,4,5, Ben W Dulken^1,6

¹Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.

Nature

|May 18, 2017

概括

编程细胞死亡蛋白1 (PD-1) 和其配体 (PD- L1) 疗法可以通过增强巨细胞灭菌来向癌症. 这项研究揭示了与瘤相关的巨细胞的PD-1表达,这表明了新的治疗机制.

科学领域:

免疫学
癌症学
细胞生物学

背景情况:

编程细胞死亡蛋白1 (PD-1) 和它的配体 (PD-L1) 是免疫耐受性的关键调节剂,瘤经常利用它们来逃避免疫监测.
目前针对PD-1/PD-L1途径的癌症免疫疗法主要集中在T细胞激活上,对它们对瘤相关巨细胞 (TAM) 的影响的了解有限.

研究的目的:

研究PD-1在TAM中的作用和表达,并确定PD-1/PD-L1阻断对癌症模型中的巨功能的影响.

主要方法:

从小鼠癌症模型和人类癌症中分析TAM中的PD-1表达.
在小鼠癌症模型中的PD-1/PD-L1通路的体内阻塞.
对巨细胞细胞活动,瘤生长和动物生存的评估.

主要成果:

小鼠和人类的TAM都表达PD-1,随着癌症的进展而增加表达.
瘤细胞的PD-1表达与它们对瘤细胞的吞能力有负相关性.
在体内,PD- 1/ PD- L1阻塞增强了TAM细胞,减少了瘤生长,并以巨细胞依赖的方式改善了生存率.

结论:

在调节TAM功能方面,PD-1/ PD- L1通路发挥着直接作用,影响抗瘤免疫力.
不仅通过T细胞激活,PD-1/ PD- L1阻塞还可以通过增强巨细胞介导的细胞化产生抗癌作用.
这些发现对优化针对PD-1/PD-L1轴的癌症免疫治疗策略具有重要意义.

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