Clinical outcomes and influencing factors of PD‑1/PD‑L1 in hepatocellular carcinoma (Review)

Abstract

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. Contents 1. Introduction 2. Listed drugs 3. Listed drugs in China 4. Influencing factors 5. Discussion 6. Conclusions

The advanced development of molecular targeted therapy for hepatocellular carcinoma

“…The overexpression of PD-L1 has been detected in the solid tumor microenvironment, including in HCC. Checkpoint inhibitors are antibodies that activate T cell-mediated antitumor responses by selectively blocking the checkpoint receptors PD-1 and PD-L1 140 .…”

A Meta-Analysis of Efficacy and Safety of PD-1/PD-L1 Inhibitors in Triple-Negative Breast Cancer

“…Immunotherapy with PD-1/PD-L1 inhibitors is a new and highly appreciated anticancer immunotherapy that reactivates the body's immune system to defend against cancer cells by blocking the PD-1/PD-L1 signaling pathway [8,9]. Currently, the marketed PD-1 inhibitors including nivolumab, pembrolizumab, and tislelizumab are mainly used for the treatment of melanoma and non-small-cell lung cancer, and their efficacy against renal cell carcinoma, bladder cancer, and Hodgkin's lymphoma is still under large-scale clinical trials [10,11]. Atezolizumab, durvalumab, and avelumab are PD-L1 inhibitors that have been clinically approved for the treatment of urothelial carcinoma, and many other drugs are currently undergoing early clinical trials [12,13].…”

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China

“… 3 In advanced HCC, radical surgery becomes infeasible as the tumor has spread beyond the liver. 4 For more than one decade, sorafenib is the only systemic therapy to improve the survival of advanced HCC. 5 However, the median survival of advanced HCC was prolonged by fewer than 3 months from sorafenib, and less than 5% of patients achieved an objective response rate (ORR).…”