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通过单细胞分析确定质瘤透T细胞中的抑制性CD161受体

Nathan D Mathewson¹, Orr Ashenberg², Itay Tirosh³

¹Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.

|February 16, 2021

概括

使用单细胞RNA测序分析了扩散性质瘤中的T细胞. 研究人员确定CD161是一种抑制受体,当被阻断时,会增强T细胞对质瘤的抗瘤活性.

科学领域:

免疫学
癌症学
基因组学

背景情况:

对于癌症免疫疗法的有效性至关重要.
它们在扩散性质瘤中的基因表达在很大程度上没有特征.
了解T细胞的作用对于开发新的质瘤疗法至关重要.

研究的目的:

测定质瘤中T细胞的基因表达和克隆构成.
识别质瘤中参与抗瘤免疫的T细胞子集和分子点.
探索自然杀手 (NK) 细胞基因和受体作为质瘤治疗点的潜力.

主要方法:

单细胞RNA测序 (RNA-seq) 在31名IDH野生型质母细胞瘤和IDH突变质母细胞瘤的瘤透T细胞上进行.
分析包括基因表达概况和T细胞克隆扩张的评估.
功能性研究涉及KLRB1基因失活和CD161阻断的体外和体内实验.

主要成果:

鉴定出具有细胞毒性和自然杀手 (NK) 细胞基因共同表达的T细胞子组是潜在的抗瘤效应体.
NK基因KLRB1 (编码CD161) 被确定为克隆扩展T细胞的候选抑制受体.
基因失活KLRB1或CD161阻断显著增强T细胞介导的质瘤细胞在体外和抗瘤功能在体内.
在其他人类癌症中也发现了KLRB1及其相关的转录程序.

结论:

这项研究提供了结质瘤内T细胞的综合图谱.
CD161和其他NK细胞受体是增强基于T细胞的质瘤免疫疗法的有前途的治疗点.
向KLRB1/CD161可能为治疗质瘤和潜在的其他癌症提供一种新的策略.

关键词:

CD161 其他发生IDH突变的质瘤一个T细胞质母细胞瘤一个细胞RNA-seq

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