上游开放的读取框架翻译增强了 mitotically 停止的癌细胞中的免疫性呈现
Alexander Kowar1,2, Jonas P Becker3,4, Rossella Del Pizzo1,2
1Translational Control and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nature communications
|August 27, 2025
概括
癌细胞通过增强特定基因区域的翻译来利用细胞分裂,从而为免疫细胞创造目标. 用线粒抑制剂向这些上游开放的读取框架 (uORF) 可以改善癌症免疫治疗.
科学领域:
- 分子生物学
- 癌症研究
- 免疫学
背景情况:
- 分裂是癌症治疗的关键细胞循环阶段.
- 药物耐药性和在转化过程中抑制的翻译带来了挑战.
- 在细胞分裂过程中,非正规转化在癌细胞中持续存在.
研究的目的:
- 在癌细胞中研究核糖体的再分配和转化调节.
- 探索线性转化对癌细胞表面抗原呈现的影响.
- 评估针对癌症免疫疗法的线粒转化治疗潜力.
主要方法:
- 分析线性癌细胞中的核糖体分布.
- 上游翻译开放式读取框架 (uORF) 和上游重叠开放式读取框架 (uoORF) 的识别和量化.
- 对新抗原和T细胞介导的癌细胞杀死试验的人类白细胞抗原 (HLA) 呈现的评估.
主要成果:
- 线性癌细胞向5'未翻译区域 (5' UTR) 和编码序列 (CDS) 呈现核糖体再分配.
- 这种重新分配有助于翻译成千上万的uORF和uoORF.
- 甲基抑制剂治疗增加了来自uORFs/uoORFs的非正规的呈现,刺激T细胞的反应.
结论:
- 在细胞分裂过程中向uORF/uoORF转化提供了一种增强癌症免疫疗法的新方法.
- 线粒体抑制剂与向uORF/uoORF衍生的表位体的疗法相结合,可以改善免疫识别和瘤消除.
- 这种方法有望克服耐药性并改善癌症治疗结果.
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