HEPATOCELLULAR CARCINOMA: CURRENT AND PROSPECTIVE IMMUNOTHERAPEUTIC STRATEGIES

Hepatocellular carcinoma (HCC) is a highly lethal and the most common primary liver cancer with increasing worldwide incidence. Pathogenesis of HCC is immune mediated, however, not completely understood. Chronic low-grade inflammation alters both innate and adaptive immune responses. As a result tolerogenic environment is established in damaged organ. Up to date, incomplete understanding of HCC pathogenesis and the extend of biomarker variability among patients represent the major obstacle for early diagnosis and for the choice of effective treatment. Among current treatment options for HCC, thermal ablation strategy, which in addition to cancer eradication provides adjuvant/"danger"signal to the patient's immune cells, has demonstrated its active immunotherapeutic effect. In ongoing phase I/II clinical trials, tumor antigen loaded dendritic cell (DC)-based vaccines as well as tumor-specific cytotoxic T cells are being tested. Genetically redirected T cell therapy and more refined autologous vaccines are still awaiting approaches in HCC. The topic of this review focuses on current and bench-to-bedside immunotherapeutic strategies for HCC and discusses their advantages and limitations in clinic. We also weight up several prospective immunotherapeutic approaches which in theory have the potential for further implication in HCC. Combination of the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression ought to be a key objective in these future developments.