Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death since most patients are diagnosed at advanced stage and the current systemic treatment options using molecular-targeted drugs remain unsatisfactory. However, the recent success of cancer immunotherapies has revolutionized the landscape of cancer therapy. Since HCC is characterized by metachronous multicentric occurrence, immunotherapies that induce systemic and durable responses could be an appealing treatment option. Despite the suppressive milieu of the liver and tumor immunosurveillance escape mechanisms, clinical studies of checkpoint inhibitors in patients with advanced HCC have yielded promising results. Here, we provide an update on recent advances in HCC immunotherapies. First, we describe the unique tolerogenic properties of hepatic immunity and its interaction with HCC and then review the status of already or nearly available immune checkpoint blockade-based therapies as well as other immunotherapy strategies at the preclinical or clinical trial stage.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and poses a serious health problem worldwide [1]
Many clinical trials have been conducted for immune checkpoint inhibitors (ICIs) monotherapies in HCC (Table 1) and the first to be approved by the FDA was the anti-PD-1 monoclonal antibodies (mAbs) nivolumab
Cancer immunotherapy has been a significant breakthrough in cancer treatment in recent years and there has been growing interest regarding its application in HCC
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and poses a serious health problem worldwide [1]. The recent development of cancer immunotherapies using immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) has dramatically changed the landscape of cancer therapy and was awarded the. Several monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or its ligand programmed cell death-ligand 1 (PD-L1) have been approved by the FDA for various types of cancers [5]. Several ICI therapies targeting PD-1/PD-L1 and CTLA-4 have already demonstrated promising activity against HCC and manageable safety in clinical trials, have been approved by the FDA. We first provide an overview of the unique intrinsic immunotolerant environment of the liver and the immune evasion mechanisms of HCC, and review recent advances in different immunotherapy approaches and their combinations for treating HCC
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