Pioneering precision: The evolution of immunotherapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality. Systemic treatment is a central pillar for the clinical management of HCC, which has been transformed by the arrival of immunotherapy in recent years. The established targets of today's immunotherapeutic options are PD-1, PD-L1, CTLA-4, and VEGF. Combinations of antibodies inhibiting PD-1/PD-L1 + VEGF and PD-1/PD-L1 + CTLA-4, respectively, have received approval and represent the current standard-of-care in the first-line setting. Immunotherapy for HCC has so far been confined to the advanced stage, but is currently being evaluated in earlier stages, too. Molecular biomarkers and classifications have been developed to guide treatment selection, but have not yet been adopted in routine clinical practice. In addition, several novel immunotherapeutic targets have been identified, and treatments exploiting those targets are currently at early as well as late stages of clinical development. Herein, we review this evolution of immunotherapy for HCC, which holds the potential for increasing therapeutic precision and thus for maximizing the benefit of patients while simultaneously reducing their risk of harm.