通过 ACOD1 枯竭进行代谢重编程,可增强固体瘤中人类诱导的多能干细胞衍生的 CAR-巨细胞的功能
Xudong Wang1,2, Siyu Su2,3, Yuqing Zhu1,4
1Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Nature communications
|September 18, 2023
概括
针对 ACOD1 增强了巨细胞的抗瘤活性. 工程化巨细胞在体内改善了癌细胞杀死和瘤抑制,提供了一种新的免疫疗法策略.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 癌症研究 癌症研究
背景情况:
- 巨细胞的亲炎症状态对于杀死瘤细胞至关重要.
- 代谢重编程影响癌症中的巨细胞功能.
研究的目的:
- 确定巨细胞亲炎状态的关键调节者.
- 评估用于癌症免疫治疗的ACOD1贫乏巨细胞.
主要方法:
- 汇集的代谢基因淘汰 CRISPR 屏幕.
- 诱导多能干细胞衍生的CAR-巨细胞 (CAR-iMAC) 平台.
- 在体外和体内癌症模型 (卵巢,胰腺).
主要成果:
- ACOD1的淘汰会促进持续的巨细胞的炎症性两极分化.
- 缺乏ACOD1的CAR-iMAC增强了ROS的产生,细胞化和细胞毒性.
- 在CAR-iMACs中的ACOD1枯竭抑制瘤并增加小鼠模型中的存活率.
- 与ACOD1-贫的CAR-iMAC和ICI联合治疗显示出协同作用的抗瘤效应.
结论:
- ACOD1是巨细胞代谢状态和炎症功能的关键调节者.
- 代谢工程的CAR-iMACs显示出强大的抗瘤能力.
- 向ACOD1为癌症免疫疗法和采用细胞移植疗法提供了一个有前途的战略.
相关概念视频
Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
iPS Cell Differentiation
2.7K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.7K
Induced Pluripotent Stem Cells
4.1K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.1K


