Leone Patrizia, Solimando Antonio Giovanni, Fasano Rossella, Argentiero Antonella, Malerba Eleonora, Buonavoglia Alessio, Lupo Luigi Giovanni, De Re Valli, Silvestris Nicola, Racanelli Vito
Unit of Internal Medicine "Guido Baccelli", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, 70124 Bari, Italy.
IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
Vaccines (Basel). 2021 May 20;9(5):532. doi: 10.3390/vaccines9050532.
Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials.
肝细胞癌（HCC）是最常见的癌症之一，也是全球第四大死因。通常，HCC在因慢性损伤或炎症而严重受损的肝脏中发生。肝移植、肝切除术、射频消融（RFA）、经动脉化疗栓塞（TACE）以及基于酪氨酸蛋白激酶抑制剂的靶向治疗是最常见的治疗方法。后者作为主要选择已使用了十年。然而，HCC中的肿瘤微环境具有很强的免疫抑制作用；因此，仍需要新的HCC治疗方法。肿瘤细胞和免疫细胞上免疫检查点分子如程序性死亡-1（PD-1）、细胞毒性T淋巴细胞抗原4（CTLA-4）、淋巴细胞激活基因3蛋白（LAG-3）和粘蛋白结构域分子3（TIM-3）的高表达以及高水平的免疫抑制细胞因子会诱导T细胞抑制，这是HCC免疫逃逸的主要机制之一。最近，基于使用免疫检查点抑制剂（ICIs）的免疫疗法，作为单一药物或与激酶抑制剂、抗血管生成药物、化疗药物和局部区域疗法联合使用，在HCC治疗中显示出巨大前景。本综述总结了近期的临床研究以及正在进行和即将开展的试验。
