RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Metabolic adaptation of NK cell activity and behavior in tumors: challenges and therapeutic opportunities.
Metabolic adaptation of NK cell activity and behavior in tumors: challenges and therapeutic opportunities.
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自然杀伤(NK)细胞对肿瘤微环境条件的适应深受其代谢活性的影响,而代谢活性本身又是营养物质可利用性和癌细胞自身代谢的结果。癌症中糖酵解和脂质代谢速率的升高不仅导致免疫抑制性副产物的积累,还促成了一个细胞外代谢物浓度升高的环境。这通过转录和翻译谱的改变导致NK细胞生物能量学的变化,最终影响其药理学特性并损害NK细胞反应。然而,理解驱动NK细胞免疫信号改变的代谢过程仍然既困难又严重缺乏探索。我们讨论了在稳态和肿瘤微环境(TME)中NK细胞代谢的多样而复杂的驱动因素、与其靶向性相关的挑战以及尚未探索的治疗机会。
The adaptation of natural killer (NK) cells to conditions in the microenvironment of tumors is deeply affected by their metabolic activity, itself a result of nutrient availability and the metabolism of the cancer cells themselves.
Elevated rates of glycolysis and lipid metabolism in cancers not only lead to the accumulation of immunosuppressive byproducts but also contribute to an environment of elevated concentrations of extracellular metabolites. This results in altered NK cell bioenergetics through changes in transcriptional and translational profiles, ultimately affecting their pharmacology and impairing NK cell responses.
However, understanding the metabolic processes that drive alterations in immunological signaling on NK cells remains both difficult and vastly underexplored.
We discuss the varied and complex drivers of NK cell metabolism in homeostasis and the tumor microenvironment (TME), challenges associated with their targetability, and unexplored therapeutic opportunities.
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