在前列腺癌细胞中PD-L1表达的调节通过安德罗根受体抑制而发生,因受体状态而有所不同
N Najafzade1,2, E Ozgur2, S B Gazioglu3
1Інститут післядипломної освіти у галузі медичних наук, Стамбульський університет, Стамбул, Туреччина.
Experimental oncology
|July 17, 2025
概括
使用PD-1/PD-L1阻断的前列腺癌 (PCa) 免疫疗法显示出不良结果. 这项研究表明,PCa中的编程细胞死亡配体1 (PD-L1) 表达依赖于雄激素受体,影响治疗疗效.
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:
- 针对PD-1/PD-L1轴的免疫检查点阻塞 (ICB) 疗法在前列腺癌 (PCa) 中有效性有限.
- 免疫治疗的关键预测标志物PD-L1表达通常在初级PCa中较低,但在晚期较高.
- 在PCa中PD-L1表达和雄激素受体 (AR) 状态之间的关系仍然未被探索.
研究的目的:
- 研究雄激素刺激和AR抑制对PCa细胞中PD-L1表达的影响.
- 要确定PD-L1表达是否受到PCa.中的雄激素受体通路的调节.
主要方法:
- 利用LNCaP和LNCaP-AR+细胞系来评估PD-L1在二激素 (DHT) 刺激和恩扎胺 (AR抑制剂) 治疗下的表达.
- 使用标准试验量化PD-L1mRNA水平和细胞活力.
- 采用ANOVA和独立的t测试进行统计分析.
主要成果:
- DHT在LNCaP细胞中增加了PD-L1表达,而甲胺则减少了它,表明了依赖于雄激素的PD-L1调节.
- 过度表达AR的LNCaP-AR+细胞表现出较高的基底PD-L1水平,但PD-L1表达没有受到DHT或酶胺的显著改变.
- 在LNCaP-AR+细胞中引起DHT的亡,但在父细胞LNCaP细胞中没有.
结论:
- 在PCa细胞中PD-L1表达取决于雄激素受体.
- 在AR过度表达的细胞中,AR抑制不会调节PD-L1的表达.
- 结果表明AR信号与PCa中的PD-L1表达之间存在复杂的相互作用,影响免疫治疗反应.
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