Immunotherapies for hepatocellular carcinoma.

Area of Science:

• Oncology
• Immunology
• Hepatology

Background:

• Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, with increasing incidence.
• Current systemic therapies for HCC include traditional agents and newer immune-checkpoint inhibitors.
• Advances in immunotherapy have revolutionized HCC management, with several regimens approved.

Purpose of the Study:

• To review the role of the immune microenvironment in HCC response and resistance to immunotherapy.
• To describe current evidence from phase III trials on immunotherapy efficacy and adverse events in HCC.
• To discuss emerging immunotherapies for all stages of HCC.

Main Methods:

• Literature review of phase III clinical trials and studies on HCC immune microenvironment.
• Analysis of efficacy, immune-related adverse events, and aetiology-dependent mechanisms of response.
• Discussion of emerging clinical trials and biomarker development.

Main Results:

• Immunotherapies, including combinations like atezolizumab/bevacizumab and durvalumab/tremelimumab, have shown improved survival in HCC.
• Distinct immune microenvironment features and genomic signatures are associated with response to immune-checkpoint inhibitors.
• No validated biomarker currently exists to guide clinical decisions for immunotherapy in HCC.

Conclusions:

• Understanding the immune microenvironment is critical for optimizing immunotherapy in HCC.
• Further research and biomarker development are needed to personalize HCC treatment strategies.
• Emerging immunotherapies hold promise for improving outcomes across all stages of liver cancer.