在瘤微环境中,PKM2通过代谢重编程和MDSCs介导的免疫抑制来协调瘤的进展
Wenxi Liu1, Jiaqi Wu1, Xinran Zhang2
1Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China.
Frontiers in immunology
|September 15, 2025
概括
瘤细胞利用糖解,称为华堡效应,获得能量. 酸激酶M2 (PKM2) 促进细胞因子的释放,招募阻断T细胞活动的髓质衍生抑制细胞 (MDSCs),从而影响瘤的发展.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 免疫学 免疫学 免疫学
背景情况:
- 瘤微环境 (TME) 对癌症的进展至关重要.
- 瘤细胞表现出改变的能量代谢,主要是糖解 (华堡效应),即使有氧.
- 酸盐激酶 (PK) 酶调节糖解,PKM2 在癌症中起着关键作用.
研究的目的:
- 阐明酸激酶M2 (PKM2) 在瘤微环境中的作用.
- 了解PKM2如何影响TME内的免疫细胞群.
- 研究PKM2影响T细胞活动的机制.
主要方法:
- 在TME内的瘤细胞中的代谢重编程的分析.
- 研究瘤细胞中PKM2的表达和功能.
- 研究瘤细胞释放的细胞因子及其对髓质衍生抑制细胞 (MDSCs) 的影响.
- 评估MDSCs对T细胞活动的影响.
主要成果:
- 在瘤中PKM2的表达很高,并驱动糖解.
- 表达PKM2的瘤细胞释放细胞因子,从而招募MDSCs.
- 这些细胞因子的MDSC激活导致了cathepsin 囊蛋白酶的上调.
- 这一级联最终抑制T细胞活动,促进瘤的发展.
结论:
- PKM2在瘤细胞代谢和免疫逃避中发挥着重要作用.
- PKM2-细胞因子-MDSC轴是抑制抗瘤免疫力的关键机制.
- 准PKM2或其下游途径可能提供新的癌症治疗策略.
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