脂质信号强迫瘤中的Treg细胞的功能专业化
Seon Ah Lim1, Jun Wei1, Thanh-Long M Nguyen1
1Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Nature
|February 25, 2021
概括
通过向固醇调节元素结合蛋白 (SREBPs) 抑制调节性T细胞中的脂质合成,释放出抗瘤免疫力. 这种方法可以增强癌症免疫疗法而不会导致自身免疫问题,
科学领域:
- 免疫学
- 癌症生物学
- 代谢信号
背景情况:
- 调节性T (Treg) 细胞对免疫耐受性至关重要,但在瘤微环境中促进免疫抑制.
- 在癌症中准Treg细胞需要了解它们的特定功能机制.
- 固醇调节元素结合蛋白 (SREBPs) 是脂质合成和代谢信号的关键调节剂.
研究的目的:
- 研究依赖于SREBP的脂质合成和代谢信号在内Treg细胞功能中的作用.
- 确定抑制Treg细胞中的SREBP活性是否可以增强抗瘤免疫反应和癌症免疫治疗.
- 阐明SREBP信号协调Treg细胞功能和PD-1表达的分子机制.
主要方法:
- 在内Treg细胞中分析SREBP活性.
- 在Treg细胞中的SREBP分裂激活蛋白 (SCAP) 的遗传删除.
- 评估瘤生长,抗瘤免疫反应,干扰素-的产生和PD-1的表达.
- 对脂肪酸合成酶 (FASN) 和氨酸代谢途径的研究.
- 对酸-3-酶 (PI3K) 激活的分析.
主要成果:
- 在内Treg细胞中,SREBP活性上调.
- 在Treg细胞中删除SCAP抑制了瘤生长并增强了PD-1向免疫治疗.
- SCAP 缺失导致干扰素的产生增加和Treg 细胞功能受损.
- 在Treg细胞中抑制SREBP信号或PD-1信号失调的PI3K激活.
- 通过FASN合成脂肪酸有助于Treg细胞成熟和瘤生长.
结论:
- 代谢重编程,特别是SREBP驱动的脂质合成,决定了Treg细胞在瘤中的专门功能.
- 向Treg细胞中的SREBP信号是一种有前途的癌症治疗策略,可以增强抗瘤免疫力而无需自身免疫毒性.
- 了解SREBP活性,脂质代谢和免疫检查点信号之间的相互作用为治疗干预提供了新的途径.
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