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Abstract Details
Emerging Immunotherapy for Hepatocellular Carcinoma: A Guide for Hepatologists
Hepatology. 2022 Mar 7. doi: 10.1002/hep.32447. Online ahead of print.
Friedrich Foerster1, Simon Johannes Gairing1, Sumera Irie Ilyas2, Peter Robert Galle1
Author information
Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany.
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the third leading cause of cancer-related death globally. HCC comprises nearly 90% of all cases of primary liver cancer. Approximately half of all HCC patients receive systemic therapy during their disease course, particularly in the advanced stages of disease. Immuno-oncology has been paradigm shifting for the treatment of human cancers, with strong and durable anti-tumor activity in a subset of patients across a variety of malignancies including HCC. Immune checkpoint inhibition with atezolizumab and bevacizumab, an anti-vascular endothelial growth factor neutralizing antibody, has become first line therapy for patients with advanced HCC. Beyond immune checkpoint inhibition, immunotherapeutic strategies such as oncolytic viroimmunotherapy and adoptive T cell transfer are currently under investigation. The tumor immune microenvironment of HCC has significant immunosuppressive elements that may impact response to immunotherapy. Major unmet challenges include defining the role of immunotherapy in earlier stages of HCC, evaluating combinatorial strategies that employ targeting of the immune microenvironment plus immune checkpoint inhibition, and identifying treatment strategies for patients who do not respond to the currently available immunotherapies. Herein, we review the rationale, mechanistic basis and supporting preclinical evidence, and available clinical evidence for immunotherapies in HCC as well as ongoing clinical trials of immunotherapy.