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Abstract Details
The Evolving Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Treatment
Vaccines (Basel). 2021 May 20;9(5):532. doi: 10.3390/vaccines9050532.
Patrizia Leone1, Antonio Giovanni Solimando12, Rossella Fasano12, Antonella Argentiero2, Eleonora Malerba13, Alessio Buonavoglia1, Luigi Giovanni Lupo4, Valli De Re5, Nicola Silvestris12, Vito Racanelli1
Author information
1Unit of Internal Medicine "Guido Baccelli", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, 70124 Bari, Italy.
2IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
3Department of Experimental Diagnostic and Specialty Medicine, "L. and A. Seràgnoli", University of Bologna, 40138 Bologna, Italy.
4Department of General Surgery and Liver Transplantation, University of Bari, 70124 Bari, Italy.
5Immunopathology and Cancer Biomarkers-Bio-Proteomics Facility, CRO Aviano National Cancer Institute, 33081 Aviano, Italy.
Abstract
Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials.