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瘤微环境诱导切换到线粒体代谢促进免疫细胞的抑制功能

Sanjay Pandey¹, Vandana Anang², Michelle M Schumacher³

¹Department of Radiation Oncology, Montefiorke Medical Center, Bronx, NY, United States.

International review of cell and molecular biology

|October 13, 2024

概括

瘤微环境改变了免疫细胞的新陈代谢,将它们转向氧化酸化和脂肪酸氧化. 这种代谢适应会损害免疫细胞的功能,促进瘤的进展和免疫耐受性.

科学领域:

癌症生物学癌症生物学
免疫学免疫学免疫学
代谢研究研究代谢研究

背景情况:

瘤微环境 (TME) 显著影响免疫细胞功能和癌症进展.
在TME中,细胞应激和营养/氧气缺乏会诱导免疫细胞的代谢变化.

研究的目的:

为了阐明TME如何改变免疫细胞代谢.
了解代谢可塑性在TME内的免疫细胞功能中的作用.
突出线粒体代谢对免疫耐受性和瘤生长的影响.

主要方法:

代谢途径的分析,包括糖解,氧化酸化 (OXPHOS) 和脂肪酸氧化 (FAO).
研究关键的代谢调节剂,如AMP激活蛋白激酶 (AMPK),拉巴胺素的机械标 (mTOR) 和缺氧诱导因子1-α (HIF-1α).

主要成果:

在TME中有限的葡萄糖会提高AMP:ATP比率,激活AMPK并抑制mTOR和HIF-1α.
免疫细胞表现出对OXPHOS和FAO的新陈代谢转变,糖解降低.
这种新陈代谢重编程往往导致免疫细胞效应器功能被抑制.

结论:

免疫细胞的TME诱导的代谢重编程导致静止或免疫抑制的表型.
改变的线粒体代谢 (OXPHOS和FAO) 是免疫耐受性和瘤进展的关键驱动因素.
了解这些代谢适应对于开发新型癌症疗法至关重要.

关键词:

这就是AMPKK.在CART-T中,我们可以使用CAR-T.脂肪酸氧化过程中的脂肪酸氧化.葡萄糖溶解是什么? 葡萄糖溶解这就是HIF1α.在 MTOR 中,我们可以使用 MTOR.代谢过程中的代谢.线粒体动力学的动态线粒体裂变的线粒体裂变线粒体融合是什么意思?线粒体代谢的代谢过程奥克斯福斯 (OXPHOS) 是一个 T细胞耗尽的情况 T细胞的新陈代谢.

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