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 patients with HCC 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 antitumor activity in a subset of patients across a variety of malignancies including HCC. Immune checkpoint inhibition with atezolizumab and bevacizumab, an antivascular 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 affect response to immunotherapy. Major unmet challenges include defining the role of immunotherapy in earlier stages of HCC, evaluating combinatorial strategies that use 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.
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