在非小细胞肺癌中,TFEB控制了对化疗和免疫杀伤的敏感性
Muhlis Akman1, Ciro Monteleone1, Gabriella Doronzo1,2
1Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.
Journal of experimental & clinical cancer research : CR
|August 6, 2024
概括
转录因子EB (TFEB) 调节药物排放载体ABCC1和ABCA1,影响非小细胞肺癌 (NSCLC) 化学免疫治疗反应. 佐勒多尼酸通过调节新陈代谢和免疫微环境来重新敏感TFEB低的NSCLC.
科学领域:
- 分子生物学和癌症研究.
- 免疫学和癌症免疫疗法免疫学
- 药物发现和纳米医学.
背景情况:
- 在非小细胞肺癌 (NSCLC) 中,化学免疫疗法的疗效受到高ABCC1和低ABCA1转运体表达的阻碍.
- ABCA1是转录因子EB (TFEB) 的预测标,但其在NSCLC化疗免疫抵抗中的作用尚不清楚.
- 依赖异烯酸铁酸盐 (IPP) 的Vγ9Vδ2T淋巴细胞激活对于抗瘤免疫是至关重要的.
研究的目的:
- 调查TFEB,ABCC1和ABCA1表达与NSCLC患者存活率之间的相关性.
- 阐明TFEB在调节ABC载体,化学敏感性和NSCLC免疫杀伤中的功能性作用.
- 在临床前的NSCLC模型中评估zoledronic acid纳米颗粒 (NZ) 的化学免疫敏感作用.
主要方法:
- 在TCGA-LUAD和机构队列中分析TFEB/ABCC1/ABCA1表达和存活率.
- 在人类NSCLC细胞中抑制TFEB以评估ABC载体表达,化学敏感性和免疫杀伤.
- 使用单细胞RNA测序对shTFEB瘤和小鼠免疫微环境的NZ影响的评估.
主要成果:
- 低ABCA1低ABCC1高的NSCLC患者的预后最差,而高ABCA1高ABCC1低的患者的预后最好.
- TFEB作为ABCA1的转录诱导剂和ABCC1的抑制剂,影响胆固醇/IPP合成和线粒体ATP生产.
- 新西兰治疗使TFEB沉默瘤对西斯普拉丁敏感,并增强了抗瘤免疫细胞的透.
结论:
- TFEB是NSCLC中化学和免疫敏感性的关键调节者.
- TFEBlowABCA1lowABCC1高的表型预测化学疗法和免疫疗法的反应不佳.
- 佐勒多尼酸可以通过改变癌症代谢和瘤免疫微环境来重新敏感TFEB低的NSCLC.
关键词:
在ABCA1中,ABCA1是ABCA1.ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1ABCC1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1C1化学免疫耐药性 化学免疫耐药性非小细胞肺癌是非小细胞肺癌.美国联邦税务法 (TFEB)Vγ9Vδ2 T 淋巴细胞更多相关视频
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