PD-1/PD-L1 blockade therapy in hepatocellular carcinoma: Current status and potential biomarkers

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death and the sixth most prevalent cancer worldwide. However, most patients with HCC are at an advanced stage at the time of clinical diagnosis, making surgery impossible. In the past, targeted therapeutic drugs such as sorafenib and lenvatinib were the main treatments. With recent breakthroughs in medicine, immunotherapy, particularly immune checkpoint inhibitors (ICIs), has garnered interest and has been extensively studied for clinical treatment. In addition to single-agent therapies, combination regimens involving ICIs have also been developed. Despite this progress, not all patients with HCC benefit from immunotherapy. Therefore, to improve the treatment response rates, it is crucial to identify patients with HCC who are suitable for immunotherapy. The exploration and validation of markers to predict the outcomes of immunotherapeutic treatments in patients with HCC are of clinical importance. In this article, we provide a comprehensive review of research progress in immunotherapy, particularly ICIs and combination therapies, for HCC. Furthermore, we summarize the clinical indicators and tumor markers discovered in recent years to forecast immunotherapy outcomes in patients with HCC. We also outline predictive markers for the occurrence of immune-related adverse events in patients with HCC receiving immunotherapy and discuss future research directions in the immunotherapeutic treatment landscape.