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Abstract Details
The Liver Cancer Immune Microenvironment: Therapeutic Implications for Hepatocellular Carcinoma
Hepatology. 2022 Aug 21. doi: 10.1002/hep.32740. Online ahead of print.
1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
2Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, United States.
3Icahn School of Medicine at Mount Sinai, The Precision Immunology Institute, New York, NY, United States.
4Graduate School of Biomedical Sciences at Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Abstract
The liver is the sixth most common site of primary cancer in humans, and the fourth leading cause of cancer-related death in the world. Hepatocellular carcinoma (HCC) accounts for 90% of liver cancers. HCC is a prevalent disease with a progression that is modulated by the immune system. Half of the patients with HCC receive systemic therapies, traditionally sorafenib or lenvatinib, as a first-line therapy. In the last few years, immune-checkpoint inhibitors (ICIs) have revolutionized cancer therapy and have gained an increased interest in the treatment of HCC. In 2020, the combination of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) improved overall survival over sorafenib, resulting in FDA approval as a first-line treatment for advanced HCC patients. Despite these major advances, a better molecular and cellular characterization of the tumor microenvironment is still needed as it has a crucial role in the development and progression of HCC. Inflamed (Hot) and non-inflamed (cold) HCC tumors and genomic signatures have been associated with response to ICIs. However, there are no additional biomarkers to guide clinical decision-making. Other immune targeting-strategies, such as adoptive T-cell transfer, vaccination, or virotherapy, are currently under development. This review provides an overview on the HCC immune microenvironment, the different cellular players, the current available immunotherapies, and potential immunotherapy modalities.