循环中的谷氨酸酶性耗尽在癌症中具有免疫抑制作用
Monish Kumar1, Ankita Leekha1, Suman Nandy1
1William A. Brookshire Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204, USA.
iScience
|May 21, 2024
概括
谷氨酸缺乏在体外抑制癌细胞生长,但在体内增加髓质衍生抑制细胞 (MDSCs). 这表明谷氨胺代谢.
科学领域:
- 瘤微环境 免疫学 免疫学
- 癌症新陈代谢 癌症新陈代谢
- 酶治疗疗法 酶治疗疗法
背景情况:
- 癌细胞表现出谷氨酸成,但其对瘤微环境 (TME) 免疫细胞的影响仍在争论中.
- 细胞外谷氨酸在TME动态中起着至关重要的作用.
- 了解谷氨胺的作用对于开发新型癌症疗法至关重要.
研究的目的:
- 研究细胞外谷氨酸耗尽对TME内的癌症生长和免疫细胞群的影响.
- 为了评估PEGylated Helicobacter pylori gamma-glutamyl转移酶 (PEG-GGT) 对全身谷氨酸耗尽的治疗潜力.
主要方法:
- 使用PEG-GGT在乳腺癌和结肠癌的同基因小鼠模型中的循环谷氨胺的酶性耗尽.
- 在体外评估PEG-GGT对癌细胞生长的影响.
- 对TCGA人类癌症数据的分析,以得出一种谷氨酸耗尽的特征,并将其与临床结果和MDSC积累相关联.
主要成果:
- 在实验室中,PEG-GGT治疗抑制了癌细胞的生长.
- 在体内,PEG-GGT治疗增加了髓质衍生抑制细胞 (MDSC),但没有显著影响瘤生长.
- 一个与不良的临床结果和MDSC在各种人类癌症中的积累相关的谷氨胺耗尽签名.
结论:
- 细胞外的谷氨酸缺乏对TME有复杂的影响,促进MDSC的积累.
- PEG-GGT是选择性全身谷氨酸耗尽的有希望的工具,提供了一种新的治疗策略.
- 这些发现澄清了谷氨胺代谢在癌症和免疫中的综合作用.
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