Liquid biopsy to identify biomarkers for immunotherapy in hepatocellular carcinoma

The past years have witnessed the vigorous development of immunotherapy, mainly immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Indeed, ICIs have largely revolutionized the management and improved the prognosis of patients with intermediate and advanced hepatocellular carcinoma (HCC). However, biomarker-based stratification of HCC patients for optimal response to ICI treatment is still of unmet need and again, there exists the necessity to dynamically monitor treatment effect in real-time manner. The role of conventional biomarkers in immunotherapy surveillance is largely limited by spatial and temporal tumor heterogeneity whereas liquid biopsy seems to be promising to circumvent tumor heterogeneity to identify candidate patients who may response to immunotherapy, to dynamically monitor treatment effect and to unveil resistance mechanism. Herein, we provide a thorough review about the potential utility of liquid biopsy in immunotherapy for HCC and discuss its future perspectives.