Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is currently the third most common cause of cancer-related mortality. Conventional chemotherapy and molecular targeted therapy options are limited for HCC. Immune checkpoint inhibitor (ICI) therapy, targeting cytotoxic T-lymphocyte protein 4 (CTLA-4), the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), could block corresponding immunosuppressive signals and exhibit potential treatment effects for advanced HCC. Clinical trials have identified a manageable safety profile and durable antitumor responses of anti-PD-1 therapy in advanced HCC. Nonetheless, a relatively small number of responders can benefit from ICI monotherapy. Recently, the combination therapy including ICI + ICI, ICI + Tyrosine kinase inhibitors (TKIs) and ICI + loco-regional approaches have been tested showing improved efficacy over ICI monotherapy.
Despite the emergence of immunotherapy in the treatment of HCC, many underlying mechanisms remain unknown: Finding predictive biomarkers that will either enrich for responders or identify those with poor tolerability is of critical importance. Either tumor-specific factors such as level of immune activation, or host factors such as the gut microbiome, or HLA heterogeneity need further investigation. The role of ICIs in the surgical setting remains unknown. Most studies focus on advanced HCC, and the application of ICIs in the adjuvant or neoadjuvant setting is lacking. The optimal combination therapy model (combination with different drugs and loco-regional therapies) would be also worth further exploration. Lastly, liquid biopsies have been developed rapidly in recent years, offering a minimally invasive tool for therapy stratification and monitoring. Although not yet routinely used in clinical practice, circulating tumor cells, cell-free DNA, as well as proteins and cytokines detected in plasma have great potential in the field of response prediction, relapse, and adverse prediction. However, whether blood tumor mutational burden (TMB) or PD-L1 expression in circulating tumor cells could be used as biomarkers in immunotherapy, especially in combination therapy for HCC patients remains unknown.
In this Research Topic, we will provide an overview of the immune anatomy and potential underlying immune mechanisms of HCC, the potential predictive biomarkers selected by liquid biopsy, and current clinical developments in this field. We welcome submissions of Original Research and Review articles focusing on immunotherapy in HCC, including those on using immunotherapy to target cancer stem cells.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is currently the third most common cause of cancer-related mortality. Conventional chemotherapy and molecular targeted therapy options are limited for HCC. Immune checkpoint inhibitor (ICI) therapy, targeting cytotoxic T-lymphocyte protein 4 (CTLA-4), the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), could block corresponding immunosuppressive signals and exhibit potential treatment effects for advanced HCC. Clinical trials have identified a manageable safety profile and durable antitumor responses of anti-PD-1 therapy in advanced HCC. Nonetheless, a relatively small number of responders can benefit from ICI monotherapy. Recently, the combination therapy including ICI + ICI, ICI + Tyrosine kinase inhibitors (TKIs) and ICI + loco-regional approaches have been tested showing improved efficacy over ICI monotherapy.
Despite the emergence of immunotherapy in the treatment of HCC, many underlying mechanisms remain unknown: Finding predictive biomarkers that will either enrich for responders or identify those with poor tolerability is of critical importance. Either tumor-specific factors such as level of immune activation, or host factors such as the gut microbiome, or HLA heterogeneity need further investigation. The role of ICIs in the surgical setting remains unknown. Most studies focus on advanced HCC, and the application of ICIs in the adjuvant or neoadjuvant setting is lacking. The optimal combination therapy model (combination with different drugs and loco-regional therapies) would be also worth further exploration. Lastly, liquid biopsies have been developed rapidly in recent years, offering a minimally invasive tool for therapy stratification and monitoring. Although not yet routinely used in clinical practice, circulating tumor cells, cell-free DNA, as well as proteins and cytokines detected in plasma have great potential in the field of response prediction, relapse, and adverse prediction. However, whether blood tumor mutational burden (TMB) or PD-L1 expression in circulating tumor cells could be used as biomarkers in immunotherapy, especially in combination therapy for HCC patients remains unknown.
In this Research Topic, we will provide an overview of the immune anatomy and potential underlying immune mechanisms of HCC, the potential predictive biomarkers selected by liquid biopsy, and current clinical developments in this field. We welcome submissions of Original Research and Review articles focusing on immunotherapy in HCC, including those on using immunotherapy to target cancer stem cells.
