瘤微环境中的骨髓系衍生抑制细胞减少脱蛋白1的表达,以提高免疫抑制活性
Jianghua Zhao1, Min Gu2, Yu Zhang2
1Department of Medicine, Jingjiang Traditional Chinese Medicine Hospital, Taizhou, 214504, China.
Biochemical and biophysical research communications
|July 20, 2024
概括
骨髓衍生抑制细胞 (MDSC) 中脱蛋白1 (UCP1) 的降低促进结直肠癌的进展. 在MDSC中UCP1缺乏会增强其免疫抑制活性,帮助瘤逃脱.
科学领域:
- 线粒体生物学 线粒体生物学
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 解蛋白1 (UCP1) 调解热生成,并与代谢疾病和癌症有关.
- 骨髓系衍生抑制细胞 (MDSCs) 在瘤微环境 (TME) 中积聚,并表现出免疫抑制活性.
研究的目的:
- 在结直肠癌的背景下,研究UCP1在MDSC中的作用.
- 确定MDSCs中改变的UCP1表达如何影响瘤进展和免疫抑制.
主要方法:
- 从结直肠癌患者和小鼠模型中MDSC中UCP1表达的分析.
- 在UCP1-淘汰赛和条件淘汰赛小鼠中评估瘤进展.
- 评估MDSC功能,包括对T细胞和Treg诱导的影响,ex vivo.
- 在瘤携带小鼠中使用α-DR5的MDSCs的消耗.
主要成果:
- 从结直肠癌患者的MDSC和小鼠瘤模型中观察到减少的UCP1表达.
- 在MDSC中UCP1缺陷加剧了瘤进展,并增加了瘤中MDSC的积累.
- 瘤衍生的MDSCs与减少的UCP1表达抑制了CD4+和CD8+T细胞反应和诱导调节性T细胞 (Tregs).
- 减少MDSC可以逆转促进瘤的效果.
结论:
- 在TME中的MDSCs降低了UCP1的表达,从而改变了它们的代谢概况.
- 这种代谢转变增强了MDSC的免疫抑制功能,促进了瘤的免疫逃生.
- 针对MDSC中的UCP1可能代表着结直肠癌的新疗法策略.
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