Wang Jiting, Li Jun, Tang Guiju, Tian Yuan, Su Song, Li Yaling
Department of Clinical Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Department of Traditional Chinese Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Oncol Lett. 2021 Apr;21(4):279. doi: 10.3892/ol.2021.12540. Epub 2021 Feb 10.
Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5-30%. In China, HCC seriously threatens the nation's health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC.
肝细胞癌（HCC）在全球的发病率呈上升趋势，全球5年生存率在5%至30%之间。在中国，HCC严重威胁国民健康；其发病率在所有肿瘤中排名第四，死亡率在全球位列第三。HCC的主要治疗方法是手术治疗或肝移植；然而，大多数HCC患者术后会出现复发或转移，最终导致死亡。对于晚期或不可切除的HCC，目前合适的治疗策略是经动脉化疗栓塞；然而，有限的治疗效果以及天然或获得性耐药会影响该方法的疗效。先前的研究表明，宿主细胞和髓样细胞上的PD-L1表达在PD-L1阻断介导的肿瘤消退中起重要作用。因此，需要对程序性细胞死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）进行进一步研究。包括美国、法国、英国和中国在内的国家已研发出PD-1/PD-L1阻断剂，包括纳武单抗、帕博利珠单抗、西米普利单抗、阿特珠单抗、阿维鲁单抗、度伐鲁单抗、特瑞普利单抗、信迪利单抗和卡瑞利珠单抗。值得注意的是，所有这些阻断剂在HCC中均有治疗效果及影响因素。影响PD-1临床结局的因素也已被发现，如炎症基因、特定受体和信号通路。这些因素的发现将有助于确定新的方法，如联合治疗，以减少其他因素对PD-1/PD-L1疗效的影响。索拉非尼和仑伐替尼已被批准用于晚期HCC患者的一线治疗。当一线治疗经常失败时，帕博利珠单抗以及伊匹木单抗联合纳武单抗在晚期HCC患者经索拉非尼（而非仑伐替尼）治疗后使用。因此，使用PD-1/PD-L1阻断剂的肿瘤免疫疗法在HCC治疗中展现出了良好前景，并且更多新型PD-1/PD-L1抑制剂正在研发中以对抗这种疾病。本综述讨论了PD-1/PD-L1抑制剂在HCC中的临床结果及影响因素，以期为PD-1/PD-L1抑制剂在HCC治疗中的研发和优化提供见解。
