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摘要: 肝癌是一种严重的全球健康问题，也是常见的癌症相关死亡原因。肝细胞癌（hepatocellular carcinoma, HCC）是肝癌常见的病理类型。早期HCC临床症状不明显，50%的HCC患者确诊时已处于晚期。系统全身治疗被推荐用于晚期HCC。随着分子靶向药物（索拉非尼、仑伐替尼）的发展，晚期HCC的系统全身治疗取得了一定进展，但对HCC患者生存获益仍然不大。近年来，免疫检查点抑制剂的出现改变了HCC治疗的格局，为HCC精准治疗提供了更多的可能性并展现出较好的效果。特别是阿替利珠单抗和贝伐珠单抗的联合疗法显著改善了HCC患者的生存预后，此外，过继性细胞疗法、肿瘤疫苗、溶瘤病毒和非特异性免疫治疗也已成为免疫治疗策略。本文就HCC免疫治疗的现状及发展进行概述。Abstract: Liver cancer is a serious global health problem and a common cause of cancer-related death. Hepatocellular carcinoma (HCC) is a common pathological type of liver cancer. The clinical symptoms of early HCC tend to be not obvious and 50% of HCC patients are already in the advanced stage by the time they are diagnosed. Systemic therapy is recommended for the treatment of advanced HCC. With the development of molecular targeted drugs (sorafenib and lenvatinib), some progress has been made in the systemic treatment of advanced HCC, but there is only modest benefit for the survival of HCC patients. In recent years, the emergence of immune checkpoint inhibitors has changed the overall outlook of HCC treatment, providing more possibilities for precise treatment of HCC and showing better treatment outcomes. In particular, the combination therapy of atezolizumab and bevacizumab significantly improved the survival outcomes in HCC patients. In addition, adoptive cell therapy, tumor vaccine, oncolytic viruses, and nonspecific immunotherapy have also emerged as strategies for immunotherapy. Herein, the status quo and development of HCC immunotherapy are reviewed.
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表 1 晚期肝癌免疫治疗关键临床试验结果
Table 1. Results of key clinical trials of immunotherapies for advanced hepatocellular carcinoma
Study Treatment options Clinical
trial stageOutcome ORR% mOS mPFS Other CheckMate 040[16] Nivolumab Ⅰ/Ⅱ 20 15.6 4.0 KEYNOTE-224[19] Pembrolizumab Ⅱ 17 12.9 4.9 Richard, et al[21] Pembrolizumab + lenvatinib Ⅰb 36 22 8.6 mTTP 9.7 months IMbrave 150[22] Atezolizumab + bevacizumab Ⅲ 30 19.2 6.9 DCR 74%, OS of 12 months 67%, OS of 18 months 52% ORIENT-32[24] Sintilimab + bevacizumab Ⅱ/Ⅲ 25 4.6 RESCUE[25] Camrelizumab + Apatinib Ⅱ 34.3 5.7 OS of 9 months 86.7%, OS of 12 months 74.7%, OS of 18 months 58.1%, DCR 77.1%, mDOR 14.8 months HIMALAYA[27] Durvalumab + tremelimumab Ⅲ 20.1 16.4 3.8 mDOR 22.34 months, mTTR 2.17 months,3-year survival rate 30.7% ORR: objective response rate; mPFS: median progression-free survival; mOS: median overall survival; OS: overall survival; mTTP: median time to progression; DCR: disease control rate; mDOR: median duration of response; mTTR: median response time. 
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