Abstract
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is derived mostly from a background of chronic inflammation. Multiple immunotherapeutic strategies have been evaluated in HCC, with some degree of success, particularly with immune checkpoint blockade (ICB). Despite the initial enthusiasm, treatment benefit is only appreciated in a modest proportion of patients (response rate to single agent ~20%). Therapy-induced immune-related adverse events (irAEs) and economic impact are pertinent considerations with ICB. It is imperative that a deeper understanding of its mechanisms of action either as monotherapy or in combination with other therapeutic agents is needed. We herein discuss the latest developments in the immunotherapeutic approaches for HCC, the potential predictive biomarkers and the rationale for combination therapies. We also outline promising future immunotherapeutic strategies for HCC patients.
Highlights
Cancer immunotherapy is a rapidly evolving field, which has revolutionized the treatment landscape in oncology this past decade [1]
immune checkpoint blockade (ICB) have been the focus of cancer immunotherapy due to its promising outcomes across multiple advanced solid malignancies, including hepatocellular carcinoma (HCC) [4,5]
We summarize the key biomarkers from intratumoral tissues and extratumoral tissues in Table 2 and provide evidence and perspectives, where available, on HCC
Summary
Cancer immunotherapy is a rapidly evolving field, which has revolutionized the treatment landscape in oncology this past decade [1]. A variety of strategies have been explored: cytokine administration, cancer vaccines, adoptive cellular therapy, and immune checkpoint blockade (ICB) [3]. ICB have been the focus of cancer immunotherapy due to its promising outcomes across multiple advanced solid malignancies, including hepatocellular carcinoma (HCC) [4,5]. Before the emergence of immunotherapy, therapeutic development in advanced HCC has been limited partly due to its complex and heterogeneous disease etiologies [10]. 15–25% of these ICB-treated patients experienced grade 3/4 treatment or immune-related adverse events (TRAEs or irAEs), such as rash, pruritus, diarrhea, and an increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) [11,12]. A better understanding of mechanistic properties of ICB and predictive biomarkers of response and toxicities is crucial for improved treatment in HCC.
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