CTG启动的隐形翻译 上游和下游的正规ATG启动Codon通过TLR刺激得到增强,并诱导小鼠的瘤回归
Ziye Song1, Youkyung Lim1, Anneloes van Krimpen2
1Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Cancer immunology research
|June 3, 2025
概括
非正典翻译可以从替代的起始编码子创建神秘的抗原,增强癌症免疫疗法. 这项研究表明,神秘的抗原表达是独立于位置的,有效地向瘤,延迟进展.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 细胞毒性T淋巴细胞 (CTLs) 在MHC I类分子上识别病毒或瘤.
- 非正规的翻译,在非正规的起始编码子启动,产生神秘的多.
- 隐秘的多胺存在于MHC I类,是潜在的癌症免疫治疗标.
研究的目的:
- 研究CTG启动的开放读取 (ORF) 与正规的ATG启动编码子相对定位对神秘抗原表达的影响.
- 评估神秘抗原在癌症免疫治疗中的潜力.
主要方法:
- 生成的不朽的老鼠祖先细胞 (HoxB8) 具有编码CTG驱动SIINFEKL (S8L) 表位的微基因结构,在ATG驱动的上或下游.
- 用托尔类受体激动剂治疗细胞以刺激先天免疫力.
- 评估了T细胞杀死表达神秘S8L的瘤细胞在体外和体内瘤进展.
主要成果:
- 天生的免疫刺激增强了CTG-S8L翻译,无论其与ATG启动的ORF相对的位置如何.
- 下游CTG-S8L翻译是通过漏洞扫描或重新启动发生的.
- 通过T细胞在体外有效杀死表达S8L密码的瘤细胞,表达S8L密码的瘤的小鼠表现出延迟的进展.
结论:
- 在先天免疫刺激后,非正规的启动码子驱动的神秘抗原翻译是位置独立的.
- 隐秘的抗原,即使在低表达水平,也可以被T细胞有效准.
- 隐秘抗原翻译为开发新型癌症免疫疗法提供了一个有希望的途径.
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