CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
一种来源于真菌的环肽通过靶向 ZAP70 和 SREBP1 增强 Th9 介导的抗肿瘤免疫
英文原题：A fungi-derived cyclic peptide enhances Th9-mediated antitumor immunity by targeting ZAP70 and SREBP1.
查看英文原题
A fungi-derived cyclic peptide enhances Th9-mediated antitumor immunity by targeting ZAP70 and SREBP1.
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中文摘要
过继性细胞治疗（ACT）依赖于持久且功能性的T细胞来介导肿瘤清除。Th9细胞是一种代谢适应性强的CD4+ T细胞亚群，具有强持久性但细胞毒性有限。在此，我们鉴定出内芝肽A（EpA），一种从灵芝相关内生真菌中分离的环肽，作为Th9细胞分化的强效增强剂。EpA促进了一种细胞毒性Th9表型，并增强了线粒体功能和代谢适应性。在机制上，EpA双重靶向ZAP70和SREBP1，将T细胞受体信号激活与脂质代谢抑制偶联。经EpA处理的Th9细胞介导了强效的、CD8+ T细胞依赖性肿瘤控制，并在体内增强了人Th9 CAR-T 细胞治疗的疗效。这些发现确立了EpA作为一种独特的环肽，可重编程Th9细胞，并提供了一种提高ACT疗效的潜在方法。
展开英文摘要原文
Adoptive cell therapy (ACT) relies on durable and functional T cells to mediate tumor clearance. Th9 cells are a metabolically fit CD4+ T cell subset with strong persistence but limited cytotoxicity.
Here, we identified endomelipeptide A (EpA), a cyclic peptide isolated from Ganoderma lucidum-associated endophytic fungi, as a potent enhancer of Th9 cell differentiation. EpA promoted a cytotoxic Th9 phenotype with enhanced mitochondrial function and metabolic fitness.
Mechanistically, EpA dually targeted ZAP70 and SREBP1, coupling T cell receptor signaling activation with lipid metabolism suppression. EpA-treated Th9 cells mediated robust, CD8+ T cell-dependent tumor control and enhanced the efficacy of human Th9 CAR T cell therapy in vivo.
These findings establish EpA as a distinct cyclic peptide that reprograms Th9 cells and provides a potential approach to boost ACT efficacy.
论文信息
- 作者
- Zhao W、Zhou Y、Chen Y、Sun Y、Tang J、Zhu Y、Ren J、Du T
- 单位
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and.
- 文献类型
- 非美国政府资助研究
- 期刊
- The Journal of clinical investigation2026 Feb 2
- 原文标识
- PubMed 41364522 · DOI 10.1172/JCI196907
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