UPP1通过诱导免疫抑制微环境促进肺腺癌的进展
Yin Li1, Manling Jiang2, Ling Aye3
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Nature communications
|February 8, 2024
概括
肺腺癌瘤细胞中的高UPP1表达促进了免疫抑制性瘤微环境 (TME). 这种UPP1活动抑制CD8+T细胞,并表明对特定向疗法的敏感性.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 瘤微环境 (TME) 显著影响肺腺癌 (LUAD) 的进展.
- 了解LUAD的分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 使用整合性单细胞RNA测序 (scRNA-seq) 调查UPP1在LUAD TME中的作用.
- 在LUAD中识别免疫抑制的分子驱动因素和潜在的治疗点.
主要方法:
- 来自117个LUAD患者样本 (377,574个细胞) 的scRNA-seq数据的综合分析.
- 通过飞行时间 (CyTOF) 分析,scRNA-seq与大量基因表达,细胞因子阵列和细胞计的相关性.
- 使用患者衍生器官 (PDO) 进行验证,以评估药物敏感性.
主要成果:
- 识别了UPP1高瘤细胞在侵袭前面,与免疫抑制TME组件相关.
- UPP1的上调会通过PI3K/AKT/mTOR途径增加免疫抑制性细胞因子 (例如TGF-β1) 和PD-L1的表达,抑制CD8+ T细胞.
- 在PPO模型中,UPP1高LUAD瘤对Bosutinib和Dasatinib的敏感性增加.
结论:
- 通过调节TME,UPP1在LUAD中发挥着显著的免疫抑制作用.
- 这些发现提供了对LUAD分子特征的见解,并支持UPP1作为治疗点.
- 开发针对 LUAD 中 UPP1 的个性化治疗策略的潜力.
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