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瘤免疫微环境的器官模型

James T Neal¹, Xingnan Li¹, Junjie Zhu²

¹Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.

|December 15, 2018

概括

这项研究引入了一种新的空气-液体接口方法,用原生免疫细胞培养患者衍生器官,成功模拟癌症免疫治疗反应,并实现个性化治疗测试.

科学领域:

癌症学
免疫学
生物技术

背景情况:

实验室癌症模型通常缺乏复杂的瘤微环境 (TME).
与内源性瘤透性淋巴细胞 (TILs) 共同培养瘤上皮质仍然具有挑战性.
对于有效的癌症研究和免疫疗法开发而言,对TME的准确回顾至关重要.

研究的目的:

开发一种用于在完整的免疫微环境下繁殖患者衍生的有机物 (PDO).
验证这些器官在癌症免疫疗法反应模型中的有用性.
建立一个个性化免疫疗法测试平台.

主要方法:

使用空气-液体接口 (ALI) 方法从人类和小鼠瘤中传播PDO.
在有机体内集成的内源性免疫细胞 (T细胞,B细胞,NK细胞,巨细胞).
用于基因表达和免疫库分析的单细胞测序.
使用抗PD-1和抗PD-L1疗法模拟免疫检查点阻塞 (ICB).

主要成果:

通过ALI方法,成功地产生了来自100多个活检的原生免疫细胞.
单细胞分析证实,PDO TILs保留了原始的瘤T细胞受体 (TCR) 光谱.
PDO精确模拟了ICB,证明了瘤抗原特异性TIL的扩张和激活.
在PDO的治疗干预引起显著的瘤细胞毒性.

结论:

带有内源性免疫层的器官繁殖提供了一个强大的TME模型.
这种方法使得有效的体外免疫瘤研究成为可能.
促进个性化免疫疗法测试和药物开发.

关键词:

美国保护产品名称 T细胞受体美国癌症检查点抑制剂免疫疗法有机物一个细胞RNA-seq 透瘤的淋巴细胞

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