AMPK激活诱导AML中的免疫细胞死亡
Johanna Mondesir1,2, Margherita Ghisi3,4, Laura Poillet3,4
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
使用GSK621激活腺5'-单酸盐激活蛋白激酶 (AMPK),可增强针对急性髓性白血病 (AML) 的免疫反应. 这种方法促进免疫细胞死亡,为AML免疫疗法提供了一条新的途径.
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:
- 全基性造血干细胞移植 (allo-HSCT) 改善了急性髓性白血病 (AML) 的存活率,但面临限制.
- 目前针对AML的免疫疗法受到白血病免疫逃生机制的阻碍.
- 需要新的免疫刺激策略来克服这些挑战.
研究的目的:
- 研究激活腺5'-单酸盐激活蛋白激酶 (AMPK) 作为AML的免疫刺激方法的潜力.
- 确定AMPK激活剂GSK621是否可以诱导抗白血病免疫反应.
主要方法:
- 在小鼠和人类AML细胞中激活AMPK,使用小分子GSK621.1.
- 评估对AML细胞的卡莱蒂库林 (CALR) 膜暴露.
- 对树突细胞激活和成熟的评估.
- 在小鼠AML模型中测试用GSK621治疗的白血病细胞接种疫苗的疗效.
- 研究T细胞在观察到的抗白血病效应中的作用.
主要成果:
- 在AML细胞上,GSK621治疗诱导了CALR膜暴露.
- 用GSK621治疗的AML细胞促进了树突细胞的激活和成熟.
- 用GSK621治疗的AML细胞接种疫苗在一个同基因AML模型中产生了保护作用.
- 保护作用取决于CD4/CD8T细胞.
结论:
- 通过GSK621对AMPK的药理活性诱导AML细胞中免疫细胞死亡的特征.
- 这一过程刺激了针对白血病的强有力的免疫反应,由T细胞介导.
- AMPK激活代表了增强AML免疫疗法的有希望的新目标.
更多相关视频
13:18Artificial Antigen Presenting Cell aAPC Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
相关概念视频
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
PI3K/mTOR/AKT Signaling Pathway
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
