PD-1 Blockade for Hepatocellular Carcinoma: Current Research and Future Prospects

Abstract

Antonio D’Alessio,1,2 Lorenza Rimassa,2,3 Alessio Cortellini,1,4 David James Pinato1,5 1Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, W120HS, UK; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 3Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 4Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 5Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, ItalyCorrespondence: David James PinatoDepartment of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UKTel [phone]Email [email protected]: The treatment of hepatocellular carcinoma (HCC) has witnessed radical changes over the last few years, with the introduction of immune checkpoint inhibitors (ICI) in clinical practice, namely the combination of atezolizumab plus bevacizumab as the standard of care for first-line treatment of advanced HCC. The immunosuppressive microenvironment of the chronically inflamed liver makes HCC a fertile ground for the use of ICI. This review focuses on anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAb), which have been extensively studied, as monotherapy, in combination with other ICI or with antiangiogenic agents. Currently, anti-PD-1 agents are approved by the United States Food and Drug Administration for second-line treatment in advanced HCC: nivolumab, alone or in combination with ipilimumab, and pembrolizumab. Lack of demonstration of survival benefit in first and second line led to the investigation of PD-1 agents in combination with multi-kinase inhibitors, with a number of first-line treatment regimens being actively investigated. Mounting evidence suggests a potential role of PD-1 blockade as adjuvant or neoadjuvant therapies. A key challenge remains the identification of biomarkers of response, since only a minority of patients appear to benefit from ICI.Keywords: liver cancer, immunotherapy, advanced, immune checkpoint inhibition, PD-1, angiogenesis

Keywords

• liver cancer
• immunotherapy
• advanced
• immune checkpoint inhibition
• pd-1
• angiogenesis