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

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.