雌激素受体阻塞通过改变肝脏的免疫抑制微环境来增强肝脏转移的免疫疗法
Yasmine Benslimane1,2, Kevin Amalfi3, Sara Lapin3
1Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Canada.
Cancer research communications
|July 15, 2024
概括
雌激素影响肝脏瘤的微环境,影响免疫治疗反应. 剥夺雌激素可以增强抗瘤免疫力,并增强免疫疗法,为肝转移提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 内分泌学 在内分泌学.
背景情况:
- 肝转移 (LM) 是癌症死亡的一个重要原因.
- 雌激素在肝脏瘤微环境 (TME) 中的作用及其对免疫治疗反应的影响仍然不清楚.
- 之前的研究发现雌激素是结直肠癌肝转移 (CRCLM) 中免疫抑制性TME的调节剂.
研究的目的:
- 为了研究雌激素剥夺对CRCLM中细胞因子/化学因子概况的影响.
- 评估雌激素调节对肝脏内在和适应性免疫反应的影响.
- 为了评估雌激素受体降解剂 (Fulvestrant) 与免疫检查点阻塞的组合,用于CRCLM治疗.
主要方法:
- 多重细胞因子阵列和RNAscope技术被用于分析肝脏TME.
- 使用CRCLM和胰腺管道腺癌的小鼠模型.
- 通过测量LM外生长和免疫细胞透来评估治疗疗效.
主要成果:
- 雌激素耗尽改变了肝脏的细胞因子/化学因子概况,并减少了M2巨细胞的积累.
- 雌激素缺乏增加了CD8+ T细胞和NKT细胞的透,特别是CCL5+/CCR5+表达细胞.
- 富勒弗兰特治疗增强了抗PD1免疫疗法,显著减少了小鼠的LM外生长.
结论:
- 雌激素调节免疫细胞向肝脏招募TME.
- 抑制雌激素的作用可以增强抗瘤免疫力,并增强免疫治疗的疗效.
- 与抗雌激素药物和免疫治疗的联合治疗可能有利于患有免疫治疗耐药的转移性癌症的患者.
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