RNA结合蛋白HuR重新编程免疫T细胞,并促进口腔状细胞癌
Mrinmoyee Majumder1, Harinarayanan Janakiraman1, Paramita Chakraborty2
1Department of Biochemistry and Molecular Biology, USA.
Oral oncology reports
|April 29, 2024
概括
过度表达Hu抗原R (HuR) 通过抑制免疫反应驱动口腔癌. 在头部和部状细胞癌 (HNSCC) 中抑制HuR可以提高抗瘤免疫力,并减少瘤生长.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 胡抗原R (HuR) 是一种转录后调节剂,涉及各种癌症.
- 过度表达HuR与头部和部状细胞癌 (HNSCC) 的发展有关.
- 在口腔瘤发生过程中,HuR在免疫功能障碍中的作用尚不清楚.
研究的目的:
- 调查HuR在口腔癌进展和免疫细胞功能中的作用.
- 确定是否针对HuR可以作为HNSCC的治疗策略.
主要方法:
- 利用CRISPR/Cas9创建HuR淘汰赛 (KO) 的口腔癌细胞和小鼠.
- 评估瘤形成,体积和免疫细胞群 (Tregs,CD8+ T细胞) 在体外和体内.
- 用HuR抑制剂pyrvinium pamoate来评估其治疗效果.
主要成果:
- 在口腔癌细胞中的HuR缺失阻止了瘤的形成和生长.
- 在HuR-KO瘤中,调控性T细胞 (Tregs) 减少,CD8+T细胞增加.
- HuR-KO小鼠对4NQO诱导的口腔恶性瘤和更高的IFN水平表现出耐药性.
- 皮尔维尼 pamoate 治疗通过增强 CD8+ T 细胞透,降低了瘤负担.
结论:
- 通过诱导免疫功能障碍,HuR促进了口腔瘤.
- 降低HuR水平可以增强抗瘤免疫力,这表明它有可能成为HNSCC的治疗点.
- 向HuR可能为头部和部状细胞癌提供一种新的治疗策略.
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