在患有多发性骨髓瘤的患者中,通过具有高ULK2表达的CD14+单细胞抑制T淋巴细胞
Fengping Peng1,2,3, Zhaoyun Liu4,5,6, Fengjuan Jiang1,2,3
1Department of Hematology, Tianjin Medical University General Hospital, 154 Anshan Street, Heping District, Tianjin, 300052, People's Republic of China.
Journal of translational medicine
|May 7, 2025
概括
多发性骨髓瘤 (MM) 骨髓单细胞通过ULK2.2破坏抗原呈现来抑制T淋巴细胞. 抑制ULK2可能会恢复T细胞功能,并提高MM患者的抗癌免疫疗法的疗效.
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:
- 多发性骨髓瘤 (MM) 是一种无法治愈的血细胞恶性瘤,其特征是经常复发.
- 在MM中,免疫抑制性骨髓环境阻碍了T淋巴细胞的活性,并降低了免疫治疗的有效性.
- 在MM中异常的骨髓单细胞与较差的患者结局有关.
研究的目的:
- 研究骨髓CD14+单细胞抑制多发性髓瘤T淋巴细胞活性的机制.
- 确定参与MM中单细胞介导免疫抑制的分子途径.
主要方法:
- 来自MM患者样本的单细胞RNA测序数据的分析 (GSE124310).
- 从新诊断的MM患者中检测CD14+单细胞和RNA测序.
- 在体外和体内实验,以评估单细胞-T淋巴细胞相互作用和信号通路.
主要成果:
- MM CD14+单细胞表现出MHC II信号的减少,异常数量,缺陷的抗原呈现,以及减少的共刺激分子.
- 在MM CD14+单细胞中发现了类似于自活性激酶2 (ULK2) 的Unc-51的升级表达.
- MM CD14+单细胞抑制了T淋巴细胞活性,ULK1/ULK2抑制减轻了这种活性;高ULK2单细胞在体内促进了瘤生长.
结论:
- 在MM中CD14+单细胞破坏抗原的处理和呈现,损害T淋巴细胞活性和抗瘤反应.
- 这些发现阐明了MM的免疫抑制机制,为改进的基于T细胞的免疫疗法铺平了道路.
- 在CD14+单细胞中准ULK2为多发性髓瘤提供了潜在的治疗策略.
更多相关视频
相关概念视频
T Cell Activation and Clonal Selection
539
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
539
T Cell Types and Functions
627
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
627


