为了T细胞向的输送和代谢重编程,设计了由树突细胞衍生的囊泡
Xiaoyu Yu1, Shuqi Chen1, Rong Sun1
1Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China.
ACS nano
|November 25, 2025
概括
工程外细胞囊提供离子 (Mg2+) 来恢复耗尽的T细胞,并与免疫检查点阻塞相结合时增强癌症免疫疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 瘤微环境 (TME) 抑制了抗瘤免疫力,限制了免疫治疗的有效性.
- 离子 (Mg2+) 可以增强细胞毒性T淋巴细胞 (CD8+T) 活动,但面临着传递挑战.
- 现有的Mg2+载体具有较差的生物相容性和向性,阻碍了治疗潜力.
研究的目的:
- 开发一种基于细胞外囊泡 (EV) 的工程系统,用于有针对性的Mg2+输送,以增强癌症免疫疗法.
- 研究通过工程EVs传递的Mg2+的免疫调节作用对T细胞代谢和TME内的功能.
主要方法:
- 基因改造的树突细胞过度表达MgtE (SLC41A1) 进行Mg2+封装成EV (E-DEV).
- 开发了装有Mg2+的E-DEVs (E-DEVs@Mg2+),用于向向瘤排水淋巴结 (TDLNs) 的向输送.
- 评估了E-DEVs@Mg2+对CD8+T细胞代谢 (糖解,氧化酸化) 的影响以及与免疫检查点阻塞的联合疗效.
主要成果:
- E-DEVs@Mg2+证明了TDLNs的热带性,并有效调节了T细胞代谢.
- 通过E-DEVs输送的Mg2+通过增强糖解和氧化酸化恢复了耗尽的CD8+T细胞的代谢适应性.
- 结合治疗E-DEVs@Mg2+与免疫检查点阻塞实现了协同的瘤抑制.
结论:
- 工程 dendritic 细胞衍生的 EVs (E-DEVs) 作为一个生物相容的平台,用于有针对性的 Mg2+ 输送.
- 这一策略显示出对耗尽的T细胞的代谢重编程的希望,克服TME介导的免疫抑制.
- 开发的方法为增强癌症免疫治疗疗效提供了一种新的治疗途径.
相关概念视频
Transcellular Transport of Solutes
Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
Protein Transport to the Outer Chloroplast Membrane
Chloroplast outer membrane proteins encoded by the nucleus are synthesized in the cytosol. Soon after synthesis, they bind cytosolic factors such as 14-3-3 protein and the Hsp70 chaperones that keep these precursors in an unfolded state until their translocation.
Two models describe the mechanism of precursor recognition and entry across the outer membrane through the TOC complex. Model 1 suggests the newly synthesized precursor binds to the TOC receptor 159 and forms a complex.
Two models describe the mechanism of precursor recognition and entry across the outer membrane through the TOC complex. Model 1 suggests the newly synthesized precursor binds to the TOC receptor 159 and forms a complex.
Introduction to Membrane Traffic
The ER, Golgi apparatus, endosomes, and lysosomes work in tandem to modify, sort, and package proteins and lipids. An integrated membrane trafficking network facilitates the back and forth shuttling of molecules within different organelles in the same cell or across the cell membrane.
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
Vesicular Tubular Clusters
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
Transport Across the Golgi
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
Protein Transport to the Inner Chloroplast Membrane
Proteins targeted to the inner chloroplast membrane, or plastid proteins, are transported by two general pathways: the stop-transfer and the re-insertion or post-import pathways. Most plastid proteins carry N-terminal transit sequences and internal import sequences targeting it to the specific chloroplast subcompartment. Proteins targeted by the stop-transfer pathway have internal hydrophobic sequences that inhibit their translocation into the stroma. As a result, these precursors are arrested...


