识别与巨细胞和树突细胞的乳酸调节相关的信号网络
Rapeepat Sangsuwan1,2, Bhasirie Thuamsang1, Noah Pacifici1
1Department of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Heliyon
|February 20, 2025
概括
乳酸盐是癌细胞的代谢副产物,显著改变了免疫细胞的信号传递. 这项研究揭示了乳酸如何影响树突细胞和巨细胞的关键通路,这对抗癌免疫至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 代谢重编程 代谢重编程
背景情况:
- 癌症免疫疗法显示有前途,但患者反应有限.
- 瘤代谢重编程,包括乳酸生产,有助于免疫逃避.
- 乳酸对先天免疫细胞 (如树突细胞 (DCs) 和巨细胞 (MΦs) 的影响是显著的,但不完全理解.
研究的目的:
- 确定受癌症相关乳酸盐度影响的DC和MΦ中的关键信号通路.
- 阐明乳酸盐在瘤微环境中调节先天免疫细胞功能的分子机制.
主要方法:
- 转录组分析以确定受影响的信号通路.
- 生物分子技术包括免疫阻塞,流细胞计和免疫光成像,以验证蛋白质水平的变化.
主要成果:
- 乳酸盐对DC和MΦ的信号网络产生不同的影响.
- 在DC中,乳酸主要改变STAT3,ERK和p38的MAPK信号.
- 在MΦ中,乳酸盐显著影响STAT1和GSK-3β信号通路.
结论:
- 这项研究确定了先天免疫细胞中乳酸介导的关键信号通路.
- 了解这些途径可以进一步了解瘤微环境与先天免疫相互作用的知识.
- 这些发现可能会为克服乳酸诱导癌症免疫抑制的策略提供信息.
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