衰老通过诱导免疫抑制性瘤微环境驱动免疫疗法耐药性
Damien Maggiorani1,2, Oanh Le1, Véronique Lisi1
1Centre de recherche du CHU Sainte-Justine, Montréal, QC, Canada.
Nature communications
|March 19, 2024
概括
衰老的细胞损害了癌症免疫治疗的有效性. 消除这些细胞可以恢复免疫功能并改善治疗结果,这表明老化药物可以增强免疫检查点抑制剂.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 免疫检查点抑制剂 (ICI) 在癌症治疗中表现有前途,但可能因免疫细胞功能受损而受到限制.
- 衰老细胞的积累,特别是治疗诱导衰老 (TIS),损害了癌症免疫疗法的有效性.
研究的目的:
- 为了研究衰老细胞对癌症免疫疗法疗效的影响.
- 探索老化药物克服免疫疗法耐药性的潜力.
主要方法:
- 研究是在小鼠中进行的,小鼠中积累了老化细胞,以及在治疗诱导老化 (TIS) 模型中进行的.
- 使用单细胞转录组分析来检查瘤微环境 (TME).
- 给予了老化药物ABT263 (Navitoclax),并评估了它对髓状细胞和CD8 T细胞的影响.
主要成果:
- 对免疫疗法的耐药性与瘤中CD8 T细胞积累和激活的减少相关.
- 消除衰老细胞恢复了TME中的免疫平衡,并改善了接受免疫治疗的小鼠的存活率.
- ABT263治疗逆转了髓状细胞的免疫抑制特征,并恢复了CD8 T细胞的增殖.
结论:
- 衰老细胞的积累损害了癌症免疫疗法的有效性,因为它损害了CD8 T细胞的反应.
- 消除衰老细胞,可能使用像ABT263这样的老化药物,可以恢复抗瘤免疫力.
- 在ICI之前先用老化药物进行预治疗,这可能是提高癌症免疫治疗结果的新策略.
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