Cheng Huijuan, Sun Guodong, Chen Hao, Li Yu, Han Zhijian, Li Yangbing, Zhang Peng, Yang Luxi, Li Yumin
Lanzhou University Second Hospital Lanzhou 730030, Gansu Province, China.
The Key Laboratory of The Digestive System Tumors of Gansu Province Lanzhou 730030, Gansu Province, China.
Am J Cancer Res. 2019 Aug 1;9(8):1536-1545. eCollection 2019.
Hepatocellular carcinoma (HCC) is the most common liver cancer with high morbidity and mortality worldwide. Systemic treatments with several multi-targeted tyrosine kinase inhibitors (TKIs), including sorafenib, lenvatinib, regorafenib and cabozantinib, have been widely utilized int the treatment of HCC. However, with tolerable adverse events and relative low survival time, neo or optimized therapies for advanced HCC are still urgently needed. New developed immune checkpoint inhibitors therapy have been first demonstrated effective in metastatic melanoma through against CTLA-4 or PD-1/PD-L1 to renew T cell effector function. Preclinical data indicated that interference with immune checkpoint molecules results in HCC growth suppression, suggesting it may bring hope to the HCC treatment. Several clinical trials applying monoclonal antibodies to immune checkpoint molecules demonstrated that immune checkpoint inhibitors are safe and enable durable antitumor activity in advanced HCC patients. Several published immunotherapy trials in HCC using Anti-CTLA-4 agents (tremelimumab) or anit-PD-1 agents (Nivolumab) have showed promising results, in which have similar response rate (15%-30%) and disease control rate with TKIs therapies. This article will review the on-going clinical trials associated with immune checkpoint molecules monotherapy or co, and then discuss the optimal scheme of immune checkpoint therapy for advanced HCC.
肝细胞癌（HCC）是全球最常见的肝癌，发病率和死亡率都很高。包括索拉非尼、仑伐替尼、瑞戈非尼和卡博替尼在内的几种多靶点酪氨酸激酶抑制剂（TKIs）的全身治疗已广泛应用于HCC的治疗。然而，由于存在可耐受的不良事件且生存时间相对较短，晚期HCC的新疗法或优化疗法仍迫切需要。新开发的免疫检查点抑制剂疗法首先在转移性黑色素瘤中被证明有效，通过对抗CTLA-4或PD-1/PD-L1来恢复T细胞效应功能。临床前数据表明，干扰免疫检查点分子可抑制HCC生长，这表明它可能给HCC治疗带来希望。几项应用单克隆抗体作用于免疫检查点分子的临床试验表明，免疫检查点抑制剂是安全的，并且能在晚期HCC患者中产生持久的抗肿瘤活性。几项已发表的使用抗CTLA-4药物（曲美木单抗）或抗PD-1药物（纳武单抗）治疗HCC的免疫疗法试验显示出了有前景的结果，其有效率（15%-30%）和疾病控制率与TKIs疗法相似。本文将综述正在进行的与免疫检查点分子单药治疗或联合治疗相关的临床试验，然后讨论晚期HCC免疫检查点治疗的最佳方案。
