Immunotherapy for hepatocellular carcinoma: Recent advances and future targets

Abstract

Immunotherapy is a promising approach to treating various types of cancers, including hepatocellular carcinoma (HCC). While single immunotherapy drugs show limited effectiveness on a small subset of patients, the combination of the anti PD-L1 atezolizumab and anti-vascular endothelial growth factor bevacizumab has shown significant improvement in survival compared to sorafenib as a first-line treatment. However, the current treatment options still have a low success rate of about 30%. Thus, more effective treatments for HCC are urgently required. Several novel immunotherapeutic methods, including the use of novel immune checkpoint inhibitors, innovative immune cell therapies like chimeric antigen receptor T cells (CAR-T), TCR gene-modified T cells and stem cells, as well as combination strategies are being tested in clinical trials for the treatment of HCC. However, some crucial issues still exist such as the presence of heterogeneous antigens in solid tumors, the immune-suppressive environment within tumors, the risk of on-target/off-tumor, infiltrating CAR-T cells, immunosuppressive checkpoint molecules, and cytokines. Overall, immunotherapy is on the brink of major advancements in the fight against HCC.

Keywords: Hepatocellular carcinoma; Immune checkpoint inhibitors; Immune suppression; Immunotherapy.