Treatment Options for Hepatocellular Carcinoma Using Immunotherapy: Present and Future

Abstract

Hepatocellular carcinoma (HCC) is a common cancer, and the body's immune responses greatly affect its progression and the prognosis of patients. Immunological suppression and the maintenance of self-tolerance in the tumor microenvironment are essential responses, and these form part of the theoretical foundations of immunotherapy. In this review, we first discuss the tumor microenvironment of HCC, describe immunosuppression in HCC, and review the major biomarkers used to track HCC progression and response to treatment. We then examine antibody-based therapies, with a focus on immune checkpoint inhibitors (ICIs), monoclonal antibodies that target key proteins in the immune response (programmed cell death protein 1, anti-cytotoxic T-lymphocyte associated protein 4, and programmed death-ligand 1) which have transformed the treatment of HCC and other cancers. ICIs may be used alone or in conjunction with various targeted therapies for patients with advanced HCC who are receiving first-line treatments or subsequent treatments. We also discuss the use of different cellular immunotherapies, including T cell receptor (TCR) T cell therapy and chimeric antigen receptor (CAR) T cell therapy. We then review the use of HCC vaccines, adjuvant immunotherapy, and oncolytic virotherapy, and describe the goals of future research in the development of treatments for HCC.

Keywords: Hepatocellular carcinoma; Immunotherapy; Liver cancer; Vaccines.

Fig. 1. Schematic illustration of the various approaches targeting TGF-β pathways for Hepatocellular carcinoma (HCC).

The effect of TGF-β controls both immune evasion and antitumor immunity. TGF-β, transforming growth factor beta.

Fig. 2. The bidirectional interactions between Hepatocellular carcinoma (HCC) tumor cells (image drawn in the center) and the immunosuppressive component including MDSCs, M2 macrophages, ILCs, N2 cells, NK2, Th2, Treg, NKT of the tumor microenvironment.

MDSCs, myeloid-derived suppressor cells; ILCs, Innate lymphoid cells; NK2, Natural killer; Th2, T helper 2; Treg, regulatory T cells; NKT, natural killer T.

Fig. 3. Inhibitors of immune checkpoints in hepatocellular carcinoma.

CTLA-4, Cytotoxic T-lymphocyte antigen 4.

Fig. 4. Diagram illustrating the GPC3-targeting peptide vaccination.

The picture shows the various steps involved in creating the vaccine. GPC3, glypican 3.