向核糖体重新编程瘤微环境,并增强癌症免疫疗法
Kaisa Cui1,2, Bingxin Liu3, Liang Gong4
1Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China. ksxg@foxmail.com.
British journal of cancer
|July 11, 2025
概括
阻断核糖体生物发生会重编程瘤微环境免疫细胞,增强抗癌免疫力和免疫疗法的有效性. 这种方法为治疗免疫性较差的瘤提供了新的策略.
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:
- 过度活跃的核糖体生物发生是瘤的一个关键特征,但它对瘤微环境的免疫细胞的影响尚不清楚.
- 现有的研究主要集中在癌细胞上,忽视了核糖体生物发生的更广泛的免疫调节效应.
- 核糖体影响瘤微环境中的癌细胞和非癌细胞.
研究的目的:
- 为了研究阻断细胞核糖体生物发生的免疫调节作用.
- 探索核糖体向治疗在增强抗瘤免疫力和免疫治疗反应方面的潜力.
- 为了识别受核糖体生物发生阻断影响的免疫细胞亚群.
主要方法:
- 利用CX-5461,一种选择性核糖体生物发生抑制剂,用于核糖体向治疗在免疫能力强的体内模型中.
- 在接受治疗的模型上进行单细胞RNA测序 (scRNA-seq).
- 分析了大规模的人类scRNA-seq数据,内部临床样本和试验.
主要成果:
- 核糖体抑制增加了淋巴细胞中细胞毒性颗粒的分泌,并促进了巨细胞的亲炎性重编程.
- 确定了对核糖体生物发生阻断敏感的独特免疫细胞亚群,与不良的临床结果有关.
- 在免疫检查点阻塞 (ICB) 治疗期间观察到这些敏感细胞的回归,突出了它们在免疫疗法疗效中的作用.
- 证明,核糖体向诱导免疫检查点表达 (例如,Lag3) 并使瘤对抗Lag3免疫疗法的敏感,导致显著的瘤回归和增强的抗瘤免疫反应.
结论:
- 细胞核糖体生物生成在支持瘤内的免疫抑制性非癌细胞方面发挥了以前未知的作用.
- 核糖体生物发生阻断可以恢复免疫监测,并提供新的策略,以提高ICB有效性在患有低免疫性瘤的患者.
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