免疫检查点抑制剂在肝细胞癌中的进展及展望

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Research Progress and Future Perspectives

细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte–associated antigen4,CTLA-4),程序性细胞死亡蛋白1(programmed cell death protein-1,PD-1)和程序性细胞死亡配体1(programmed cell death ligand 1,PD-L1)等免疫检查点能抑制抗肿瘤免疫应答,免疫检查点抑制剂的使用(Immune checkpoint inhibitors,ICIs)拓宽了肿瘤临床治疗理念。临床研究表明,ICIs使更多的肝细胞癌(hepatocellular carcinoma,HCC)患者生存获益,主要表现在部分患者中产生了显著且持久的应答,但同时也存在原发性或适应性耐药。HCC的ICIs联合治疗策略正在1、2或3期试验中进行评估,部分结果表明ICIs与分子靶向药物及局部治疗等联合使用为HCC治疗提供了更为有效的策略。在本综述中,我们总结了ICIs及其联合治疗的最新进展,探讨ICIs在HCC治疗中有效的预测标志物及联合模式选择。

Inhibitory checkpoints,including cytotoxic T lymphocyte?Cassociated antigen 4(CTLA-4),programmed cell death protein-1(PD-1),and programmed cell death ligand 1(PD-L1),have been identified to suppress anti-tumor immune responses in solid tumors.The application of immune checkpoint inhibitors(ICIs)have reversed immune exhaustion with promising efficacy in practice,which expanded the spectrum of clinical use.Recent output studies show immune checkpoint therapy provides survival benefit for tremendous numbers of patients with hepatocellular carcinoma(HCC).While with remarkable and durable responses in a subset HCC patients,majority of those will still develop primary non-response or adaptive resistance.The combination treatment strategies with immunotherapy is being evaluated in phase 1,2 or 3 trials in HCC,and some of the results suggested that an anti-PD-1 antibody combined with other ICIs,Tyrosine Kinase Inhibits(TKI),systemic therapy or locoregional therapy are more effective treatment strategies.In this review,we summarise recent developments in ICIsbased therapies,and speculate rational deployment of the effective predictive markers and selection of the combination therapy strategies,which should hold promise for improve the efficacy and prognosis of HCC patients.