单细胞转录组分析揭示了超重和肥胖结直肠癌中免疫抑制的情况
Guozhong Xiao1,2,3, Yihui Zheng1,2,3, Huaxian Chen1,2,3
1Department of General Surgery (Department of Coloproctology), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510655, China.
Journal of translational medicine
|February 4, 2024
概括
超重和肥胖在结肠直肠癌 (CRC) 中创造了一个更具免疫抑制性的瘤环境. 这项研究揭示了CRC细胞中明显的代谢变化,影响免疫细胞功能并提供新的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 代谢学 代谢学 代谢学
- 一个单细胞分析.
背景情况:
- 超重和肥胖是众所周知的各种癌症的风险因素,包括结肠直肠癌 (CRC).
- 将肥胖与CRC进展联系在一起的特定分子机制在很大程度上是未知的.
- 了解肥胖个体单细胞水平的CRC对于开发向疗法至关重要.
研究的目的:
- 在超重/肥胖患者中研究结直肠癌单细胞特征.
- 为了确定超重/肥胖CRC和正常体重CRC之间的免疫和代谢差异.
- 在肥胖的背景下发现驱动CRC的分子机制.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 在瘤和相邻的正常结直肠组织上进行.
- 从15名超重/肥胖患者和15名体重正常的CRC患者获得样本.
- 细胞类型进行了注释,并分析了基因表达模式,以表征免疫和代谢特征.
主要成果:
- 对192,785个细胞的单细胞分析揭示了CRC生态系统中的九种主要细胞类型.
- 超重/肥胖的CRC显示T细胞和NK细胞的细胞毒性功能受损,这是由于代谢失调造成的.
- 在超重/肥胖的CRC中观察到CD4+ T细胞上增加的免疫检查点分子,DC和B细胞下调的抗原呈现,以及功能障碍的树皮细胞.
- 瘤细胞表现出上调的葡萄糖分解和脂质代谢,影响免疫细胞功能,导致抑制性瘤-T细胞相互作用.
结论:
- 超重/肥胖CRC的特点是更具免疫抑制性的微环境.
- 显著的代谢重编程,包括增强的葡萄糖分解和脂质代谢,是超重/肥胖CRC的标志.
- 这些发现为开发新型治疗策略为肥胖的CRC患者提供了基础.
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