氨酸A2A受体是NASH相关的肝细胞癌的瘤抑制剂
Bertrand Allard1, Célia Jacoberger-Foissac1, Isabelle Cousineau1
1Centre de Recherche du Centre Hospitalier de l'Université de Montréal et Institut du Cancer de Montréal, Montreal, QC, Canada; Faculté de Pharmacie, Université de Montréal, Montreal, QC, Canada.
腺氨酸A2A受体 (A2AR) 通常可以抑制肝癌. 阻止A2AR会使肥胖,炎症和肝细胞癌 (HCC) 恶化,特别是在非酒精性脂肪肝炎 (NASH) 患者中.
科学领域:
- 免疫学 免疫学 免疫学
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
背景情况:
- 氨酸A2A受体 (A2AR) 抗剂正在用于癌症免疫疗法.
- 在肝癌 (肝细胞癌,HCC) 中A2AR的作用尚未完全理解.
研究的目的:
- 为了研究A2AR在肝细胞癌 (HCC) 发展中的功能.
- 确定A2AR抑制对肥胖,炎症和肝癌的影响.
主要方法:
- 使用Ador2a被删除的小鼠研究自发和诱导的HCC.
- 在骨髓和肝细胞中采用条件基因删除.
- 分析人类HCC患者的ADORA2A表达和临床相关性数据.
主要成果:
- 在小鼠中,Adora2a删除诱导了肥胖,非酒精性脂肪肝炎 (NASH) 和HCC.
- 骨髓细胞和肝细胞中的A2AR信号通过减少肝炎和脂肪来抑制HCC.
- A2AR封锁加剧了HCC,特别是在先前存在的NASH的背景下.
- 低ADORA2A基因表达与肝硬化,炎症和人类HCC的生存率差相关.
结论:
- 在肝脏中,A2AR具有以前未知的瘤抑制作用.
- 在NASH患者和那些患有NASH相关的HCC的人群中使用A2AR抗剂时,建议谨慎.
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