干扰CD47-SIRPα信号传递恢复了与瘤相关的髓质衍生抑制细胞的炎症功能
Carlo Zimarino1, William Moody1, Sarah E Davidson1,2
1MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
iScience
|April 5, 2024
概括
准神经质衍生抑制细胞 (MDSC) 中的信号调节蛋白α (SIRPα) /CD47信号,可以恢复抗瘤免疫力. 调节MDSC功能可以增强T细胞活性,并延迟瘤在固体癌症中的生长.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 骨髓系衍生抑制细胞 (MDSCs) 是固体瘤中的关键免疫抑制剂.
- 瘤微环境因素调节MDSC的功能和分化.
研究的目的:
- 调查SIRPα/CD47信号在调节MDSC免疫抑制性质中的作用.
- 探索针对MDSC的治疗策略,以增强抗瘤免疫力.
主要方法:
- 利用小鼠黑色素瘤模型和用造血干细胞进行体外研究.
- 分析了MDSC分化,细胞能力,免疫检查点表达和T细胞抑制.
- 研究了扰乱SIRPα信号对髓状细胞功能和抗瘤反应的影响.
主要成果:
- 瘤微环境诱导了具有强大的T细胞抑制能力的MDSC.
- 激活SIRPα/CD47可降低骨髓细胞细胞分裂并增强免疫抑制.
- 扰乱SIRPα信号恢复了MDSC细胞和抗原呈现,增加了T细胞活性.
- 对SIRPα信号的治疗向延迟了固体癌症中的瘤生长.
结论:
- 在固体瘤中,SIRPα/CD47信号传递是MDSC功能的关键调节者.
- 准髓状细胞功能,特别是SIRPα信号传递,可以克服瘤诱导的免疫抑制.
- 针对骨髓功能与免疫检查点抑制剂的联合治疗有望增强抗瘤免疫力.
更多相关视频
07:44Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
7.5K
09:57Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
Published on: January 29, 2019
22.5K
相关概念视频
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
