环氧化酶-2抑制剂通过调节性T细胞在肝细胞癌中作用的研究进展  

Advances in the role of cyclooxygenase 2 inhibitors in hepatocellular carcinoma via regulatory T lymphocytes

作　　者：郑海龙 许丙忱 刘彦琦[2] 王飞[3] Zheng Hailong;Xu Bingchen;Liu Yanqi;Wang Fei(The First Clinical College of Inner Mongolia Medical University,Hohhot 010010,China;Department of Gastroenterology,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010010,China;Department of Surgery of Sunset Gallbladder,Pancreas and Spleen,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010010,China)

机构地区：[1]内蒙古医科大学第一临床学院,呼和浩特010010 [2]内蒙古医科大学附属医院消化内科,呼和浩特010010 [3]内蒙古医科大学附属医院肝胆胰脾外科,呼和浩特010010

出　　处：《中华实验外科杂志》2024年第12期2901-2906,共6页Chinese Journal of Experimental Surgery

基　　金：国家自然基金项目(82260481);中央引导地方科技发展资金项目(2023ZY0021);内蒙古自治区科技计划项目(2022YFSH0112);内蒙古自治区卫生健康委科技计划项目(202201282);内蒙古医科大学校级项目(YKD2022MS023);内蒙古医科大学附属医院院级科研项目计划国自然培育项目(2023NYFYPY004)。

摘　　要：肝癌是全球癌症相关死亡的第三大原因, 肝细胞癌(HCC)是其中的主要类型。患者在确诊HCC时, 大部分已经失去手术切除、消融术机会。肝内免疫在HCC的发生、发展过程中起着至关重要的作用。近年随着对肝脏微环境的认识逐渐深化, 人们对HCC的治疗已经由针对癌细胞的直接治疗逐渐转移到对肝脏免疫微环境的调控。先天免疫、适应性免疫都在肝脏免疫微环境中发挥重要作用, 它们的失衡可能是HCC进展的关键因素。值得注意的是, 调节性T细胞(Tregs)在免疫调节中发挥着重要作用, 通过降低Tregs比率可以有效激活先天免疫、适应性免疫对HCC的攻击作用。环氧化酶-2(COX-2)抑制剂可能通过增强Enclysis途径(肝细胞特异性吞噬Tregs途径)和降低前列腺素E、D表达, 在降低Tregs比率中发挥重要作用。本文以COX-2抑制剂降低Tregs比率并增强先天免疫、适应性免疫以治疗HCC作为假说, 将各信号通路及作用机制进行阐述, 为中晚期肝细胞癌联合治疗提供策略。Liver cancer is the third leading cause of cancer-related deaths globally,with hepatocellular carcinoma(HCC)being the predominant type.By the time most patients are diagnosed with HCC,they have often lost the opportunity for surgical resection or ablation.The immune response within the liver plays a crucial role in the occurrence and progression of HCC.In recent years,as our understanding of the hepatic microenvironment has deepened,the treatment strategies for HCC have shifted from direct targeting of cancer cells to modulating the liver’s immune microenvironment.Both innate and adaptive immunity play significant roles in this context,and their imbalance may be a key factor in the progression of HCC.Notably,regulatory T cells(Tregs)are essential for immune regulation;reducing the frequency of Tregs can effectively activate both innate and adaptive immune responses against HCC.Cyclooxygenase-2(COX-2)inhibitors may play an important role in decreasing Treg frequencies by enhancing the Enclysis pathway(a liver-specific mechanism for phagocytosing Tregs)and reducing the expression of prostaglandins E and D.This paper hypothesizes that COX-2 inhibitors can lower Treg frequencies and enhance both innate and adaptive immunity to treat HCC.It will elaborate on the relevant signaling pathways and mechanisms involved,providing strategies for the combined treatment of advanced hepatocellular carcinoma.

关 键 词：环氧化酶-2 免疫调节T细胞 细胞免疫 肝细胞肝癌 

分 类 号：R735.7[医药卫生—肿瘤]