Immune Netw.  2020 Feb;20(1):e11. 10.4110/in.2020.20.e11.

Current Status and Future Direction of Immunotherapy in Hepatocellular Carcinoma: What Do the Data Suggest?

Affiliations
  • 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea. drpjy@yuhs.ac
  • 2Institue of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea.
  • 3Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea.
  • 4BK21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.

Abstract

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.

Keyword

Carcinoma, hepatocellular; Immune checkpoint inhibitor; Therapeutics

MeSH Terms

Antibodies
Carcinoma, Hepatocellular*
Humans
Immune System
Immunotherapy*
Ligands
Protein-Tyrosine Kinases
Receptors, Vascular Endothelial Growth Factor
T-Lymphocytes, Regulatory
Tumor Microenvironment
Antibodies
Ligands
Protein-Tyrosine Kinases
Receptors, Vascular Endothelial Growth Factor
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