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外围T细胞扩张预测瘤透和临床反应

Thomas D Wu¹, Shravan Madireddi², Patricia E de Almeida²

¹Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, CA, USA. twu@gene.com.

|February 28, 2020

概括

T细胞克隆类型在瘤和相邻组织中扩大,它们在血液中的存在有助于对抗PD-L1治疗的患者进行鉴定. 这表明持续的T细胞补充能促进癌症免疫力和治疗反应.

科学领域:

免疫学
癌症学
基因组学

背景情况:

阻断编程细胞死亡蛋白1 (PD1) 和其连接体编程细胞死亡连接体1 (PDL1) 的抗体在癌症治疗中是成功的,但机制尚不清楚.
在癌症患者中缺乏T细胞克隆型分布的定量数据,这阻碍了对瘤免疫力的理解.

研究的目的:

研究癌症患者的瘤,邻近组织和血液中的T细胞群和T细胞受体配置.
将T细胞克隆型扩张与抗PD- L1治疗的反应相关联.

主要方法:

在患者样本上进行深度单细胞RNA和T细胞受体测序.
对T细胞克隆型分布在瘤,邻近组织和外周血液的分析.
与外部数据集集集成以分析T细胞动态.

主要成果:

在瘤和正常邻近组织中发现效应型T细胞克隆型扩张的证据.
克隆型扩张的基因特征与抗PD-L1治疗的更好反应相关.
在周围血液中可以检测到扩展的克隆类型,提供一种非侵入性患者识别方法.

结论:

响应患者的瘤内T细胞由瘤外的细胞补充,表明癌症免疫周期活跃.
这种持续的补充和免疫循环加速可能与抗PD- L1治疗的临床反应有关.

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