Advances in Immunotherapy for Hepatocellular Carcinoma

SIMPLE SUMMARY: Immunotherapy for hepatocellular carcinoma (HCC) is progressing rapidly. In particular, analyses of the tumor immune environment in HCC are progressing. Moreover, custom-made immunotherapy is being considered. A new taxonomy of immune subclasses of HCC is described. A relationship between etiology and immunotherapy has also been suggested. Furthermore, interesting reports have been made on the relationship between nonalcoholic steatohepatitis-HCC and immunotherapy. Understanding the tumor immune environment is essential for implementing immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma. It is also important in managing the side effects of ICIs as well. The purpose is to summarize the progress of immunotherapy in hepatocellular carcinoma and to utilize it for future treatment. ABSTRACT: Immune checkpoint inhibitors (ICIs) aim to induce immune responses against tumors and are less likely to develop drug resistance than molecularly targeted drugs. In addition, they are characterized by a long-lasting antitumor effect. However, since its effectiveness depends on the tumor’s immune environment, it is essential to understand the immune environment of hepatocellular carcinoma to select ICI therapeutic indications and develop biomarkers. A network of diverse cellular and humoral factors establishes cancer immunity. By analyzing individual cases and classifying them from the viewpoint of tumor immunity, attempts have been made to select the optimal therapeutic drug for immunotherapy, including ICIs. ICI treatment is discussed from the viewpoints of immune subclass of HCC, Wnt/β-catenin mutation, immunotherapy in NASH-related HCC, the mechanism of HPD onset, and HBV reactivation.