Yu Su Jong
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Pharmacol Ther. 2023 Apr;244:108387. doi: 10.1016/j.pharmthera.2023.108387. Epub 2023 Mar 21.
Immunotherapy is a promising approach to treating various types of cancers, including hepatocellular carcinoma (HCC). While single immunotherapy drugs show limited effectiveness on a small subset of patients, the combination of the anti PD-L1 atezolizumab and anti-vascular endothelial growth factor bevacizumab has shown significant improvement in survival compared to sorafenib as a first-line treatment. However, the current treatment options still have a low success rate of about 30%. Thus, more effective treatments for HCC are urgently required. Several novel immunotherapeutic methods, including the use of novel immune checkpoint inhibitors, innovative immune cell therapies like chimeric antigen receptor T cells (CAR-T), TCR gene-modified T cells and stem cells, as well as combination strategies are being tested in clinical trials for the treatment of HCC. However, some crucial issues still exist such as the presence of heterogeneous antigens in solid tumors, the immune-suppressive environment within tumors, the risk of on-target/off-tumor, infiltrating CAR-T cells, immunosuppressive checkpoint molecules, and cytokines. Overall, immunotherapy is on the brink of major advancements in the fight against HCC.
免疫疗法是治疗包括肝细胞癌(HCC)在内的各种癌症的一种有前景的方法。虽然单一免疫疗法药物对一小部分患者显示出有限的疗效,但抗程序性死亡受体配体1(PD-L1)药物阿替利珠单抗和抗血管内皮生长因子药物贝伐单抗联合使用,作为一线治疗与索拉非尼相比,已显示出显著的生存改善。然而,目前的治疗方案成功率仍然很低,约为30%。因此,迫切需要更有效的HCC治疗方法。几种新型免疫治疗方法,包括使用新型免疫检查点抑制剂、创新的免疫细胞疗法如嵌合抗原受体T细胞(CAR-T)、T细胞受体(TCR)基因修饰的T细胞和干细胞,以及联合策略,正在针对HCC治疗进行临床试验测试。然而,仍然存在一些关键问题,如实体瘤中存在异质抗原、肿瘤内的免疫抑制环境、靶向非肿瘤效应的风险、浸润性CAR-T细胞、免疫抑制检查点分子和细胞因子等。总体而言,免疫疗法在抗击HCC方面正处于重大进展的边缘。