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用于癌症免疫治疗的FOXP3通过形态素介导的剪接重新编程内T_reg细胞

Yujing Li^1,2,3, Naresh Singh^3,4,5, Chuanpeng Dong³

¹Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China.

Science immunology

|August 22, 2025

概括

通过将FOXP3表达转移到一个短的异型 (FOXP3dE2) 来重新编程调节性T细胞,可以增强CD8T细胞的抗瘤免疫力. 这种方法对癌症免疫疗法具有前景.

科学领域:

免疫学
癌症学
分子生物学

背景情况:

调控性T细胞是有效抗瘤免疫的关键障碍.
FOXP3是Treg细胞功能的关键转录因子.

研究的目的:

通过FOXP3异形切换对Treg细胞进行重编程以增强抗瘤免疫力的潜力.
探索FOXP3dE2异型在癌症中的治疗含义.

主要方法:

在癌症中分析全长FOXP3 (FOXP3FL) 和短 (FOXP3dE2) 异构体.
仅表达FOXP3dE2异型的小鼠模型的生成.
使用Morpholino oligos来诱导FOXP3的第2个突变.
在体外和体内评估抗瘤活性和T细胞功能.

主要成果:

在三阴性乳腺癌中,FOXP3dE2表达与改善的患者存活率相关.
具有FOXP3dE2表达的小鼠抵抗了瘤的发展.
FOXP3dE2+ Treg细胞显示免疫抑制降低和促进CD8T细胞激活.
通过Morpholino诱导的FOXP3异构2跳转增强了抗瘤免疫力和T细胞杀伤能力.

结论:

将FOXP3表达转移到FOXP3dE2异型重新编程Treg细胞.
这种重编程将Treg细胞转化为T辅助细胞,增强CD8T细胞介导的抗瘤免疫力.
向FOXP3异型表达是一种新的癌症免疫治疗策略.

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