来自癌细胞的IL-1β逆转了非小细胞肺癌中化学免疫疗法耐药性的作用
Anaïs Perrichet1,2,3,4, Julie Lecuelle1,2,3,4, Emeric Limagne1,2,3,4
1Cancer Biology Transfer Platform, Centre Régional De Lutte Contre Le Cancer Georges-François Leclerc, Dijon, France.
Nature communications
|November 21, 2025
概括
介质素-1β (IL-1β) 的使用可以克服对肺癌化学免疫疗法的耐药性. 这涉及癌细胞衍生CXCL10,CD8T细胞的招募,并通过TXNIP激活AIM2炎症酶.
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:
- 非小细胞肺癌 (NSCLC) 通常对化疗和免疫检查点抑制剂表现出耐药性.
- 介素-1β (IL-1β) 传统上与促进肺癌生长有关.
研究的目的:
- 研究IL-1β在克服NSCLC中化疗免疫疗法耐药性的潜力.
- 阐明 IL-1β 治疗作用的基础分子机制.
主要方法:
- 利用小鼠肺癌模型来评估IL-1β的管理和过度表达效应.
- 分析了来自癌细胞的CXCL10,CD8T细胞招募和AIM2炎症酶途径.
- 对患者瘤进行了转录组分析,并进行了药物查.
主要成果:
- 在小鼠模型中,IL-1β的使用逆转了对西斯普拉丁/佩梅特克塞德/抗PD-1化疗免疫疗法的耐药性.
- 抗瘤效应是由癌细胞衍生的CXCL10调解的,CXCL10招募CD8T细胞.
- 铁素相互作用蛋白 (TXNIP) 激活AIM2炎症体触发了IL-1β和CXCL10分泌.
- 高IL1B,IL1R1,AIM2和/或TXNIP的表达与NSCLC患者更好的免疫疗法反应相关.
- 鉴定出MEK和MDM2抑制剂是TXNIP的诱导剂,可以逆转化疗免疫疗法耐药性.
结论:
- 与之前的假设相反,IL-1β在NSCLC治疗中起着有益的作用.
- 增强局部IL-1β的产生可以成为克服NSCLC化学免疫疗法耐药性的策略.
- 准TXNIP-AIM2炎症酶途径为NSCLC提供了一种新的治疗方法.
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