Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering-C (NIBGE), Faisalabad 38000, Pakistan.
Int J Mol Sci. 2024 Jun 21;25(13):6830. doi: 10.3390/ijms25136830.
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a significant global health burden, with increasing incidence rates and limited treatment options. Immunotherapy has become a promising approach due to its ability to affect the immune microenvironment and promote antitumor responses. The immune microenvironment performs an essential role in both the progression and the development of HCC, with different characteristics based on specific immune cells and etiological factors. Immune checkpoint inhibitors, including programmed death-1/programmed death-ligand 1 inhibitors (pembrolizumab, nivolumab, and durvalumab) and cytotoxic T lymphocyte antigen-4 inhibitors (tremelimumab and ipilimumab), have the potential to treat advanced HCC and overcome adverse effects, such as liver failure and chemoresistance. Phase II and phase III clinical trials highlight the efficacy of pembrolizumab and nivolumab, respectively, in advanced HCC patients, as demonstrated by their positive effects on overall survival and progression-free survival. Tremelimumab has exhibited modest response rates, though it does possess antiviral activity. Thus, it is still being investigated in ongoing clinical trials. Combination therapies with multiple drugs have demonstrated potential benefits in terms of survival and tumor response rates, improving patient outcomes compared to monotherapy, especially for advanced-stage HCC. This review addresses the clinical trials of immunotherapies for early-, intermediate-, and advanced-stage HCC. Additionally, it highlights how combination therapy can significantly enhance overall survival, progression-free survival, and objective response rate in advanced-stage HCC, where treatment options are limited.
肝细胞癌（HCC）是第六种最常见的癌症，也是一个重大的全球健康负担，其发病率不断上升，治疗选择有限。免疫疗法因其能够影响免疫微环境并促进抗肿瘤反应而成为一种很有前途的方法。免疫微环境在 HCC 的进展和发展中起着至关重要的作用，不同的免疫细胞和病因因素具有不同的特征。免疫检查点抑制剂，包括程序性死亡受体 1/程序性死亡配体 1 抑制剂（pembrolizumab、nivolumab 和 durvalumab）和细胞毒性 T 淋巴细胞相关抗原 4 抑制剂（tremelimumab 和 ipilimumab），有潜力治疗晚期 HCC 并克服不良反应，如肝衰竭和化疗耐药。II 期和 III 期临床试验分别强调了 pembrolizumab 和 nivolumab 在晚期 HCC 患者中的疗效，表现为它们对总生存期和无进展生存期的积极影响。Tremelimumab 显示出适度的反应率，但它具有抗病毒活性。因此，它仍在正在进行的临床试验中进行研究。多种药物联合治疗在生存和肿瘤反应率方面显示出潜在的益处，与单药治疗相比，改善了患者的结局，尤其是对于晚期 HCC。这篇综述讨论了免疫疗法在早期、中期和晚期 HCC 中的临床试验。此外，它还强调了联合治疗如何显著提高晚期 HCC 的总生存期、无进展生存期和客观缓解率，因为晚期 HCC 的治疗选择有限。
