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RELB重新编程耗尽的瘤透性淋巴细胞,以改善采用细胞治疗

Christian D McRoberts Amador^1,2, Rachel E Conover^2,3, Michael C Brown⁴

¹Department of Pharmacology and Cancer Biology, Duke University.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

转录因子RELB增强瘤透淋巴细胞 (TIL) 的扩张和功能. 这一发现提供了一种新的策略,通过提高T细胞的持久性和杀死能力来改善固体瘤的细胞疗法.

科学领域:

免疫学免疫学免疫学
细胞疗法细胞疗法
癌症研究癌症研究

背景情况:

瘤透性淋巴细胞 (TILs) 是固体瘤的一个有前途的细胞疗法.
目前的TIL疗法因T细胞功能障碍和有限扩张而面临挑战.
CD103+CD39+CD8+TILs显示瘤反应性,但通常表现为疲劳.

研究的目的:

为了确定人类TIL扩散的调节者.
为了提高基于TIL的癌症免疫疗法的疗效.

主要方法:

选了一个人类转录因子库,以找到TIL扩展调节器.
使用与瘤有机体和针对HER2的CAR T细胞的共同培养模型.
进行了转录基因组分析和*in vivo*老鼠异种移植研究.

主要成果:

确定RELB是人类TIL扩张的关键驱动因素,特别是CD8+T细胞.
RELB表达维持了T细胞受体多样性,并促进了记忆表型.
通过RELB工程设计的TILs显示了增强的持久性,体内瘤控制,以及改善了对患者匹配的瘤器官的杀死.

结论:

RELB作为TIL扩散和功能的强有力的调节者.
促进RELB表达是一种可行的策略,可以增强固体瘤的TIL治疗.
这种方法可以扩大基于TIL的免疫疗法的适用性和有效性.

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