在癌症中,巨细胞本体生成和重编程的轨迹
Florent Duval1,2,3, Joao Lourenco2,3,4, Mehdi Hicham1,2,3
1Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland.
iScience
|June 6, 2025
概括
在瘤相关巨细胞 (TAMs) 中禁用Dicer1促进了它们的免疫刺激功能,增强了癌症免疫疗法. 这种方法阻碍了免疫抑制性TAM的发展,改善了治疗反应.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 与瘤相关的巨细胞 (TAMs) 经常表现出免疫抑制的表型,导致免疫疗法耐药性.
- Dicer1在巨细胞分化和瘤微环境中的功能中发挥作用.
研究的目的:
- 研究TAM中Dicer1无活化的对瘤微环境和免疫治疗反应的影响.
- 确定特定的TAM亚群作为潜在的治疗点.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 用于分析Dicer1-无活化 (DKO) 和野生类型小鼠癌症模型中的TAM.
- 伪素体分析被用来推断巨细胞的发育轨迹.
- 一个正确的肺癌模型被用来评估免疫治疗的疗效.
主要成果:
- 在TAM中Dicer1的失活促进了瘤微环境的免疫刺激编程,依赖于干扰素-γ (IFNγ).
- 伪物体分析显示,Dicer1的非激活使TAM在中间状态停滞,阻止它们过渡到免疫抑制的M2类表型.
- 重编程的TAM在肺癌模型中增强了对抗血管原性免疫疗法的反应.
结论:
- 针对TAM中的Dicer1提供了一种策略,通过促进免疫刺激性巨细胞表型来克服免疫疗法耐药性.
- 循环/M2型巨体在小鼠和人类癌症中都代表了保存和潜在的选择性治疗标,特别是在免疫治疗反应不佳的患者中.
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