Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC

Area of Science:

• Hepatocellular Carcinoma (HCC) Research
• Immunotherapy and Oncology
• Biomarker Discovery

Background:

• Advanced, unresectable hepatocellular carcinoma (HCC) presents a significant clinical challenge with poor patient outcomes.
• Approved immune checkpoint inhibitors (ICIs) targeting the programmed-cell death 1 (PD-1/L1) pathway offer treatment options for advanced HCC, but patient responses are variable and unpredictable.

Purpose of the Study:

• To review the biological rationale and clinical progress of combination therapies involving ICIs for HCC.
• To discuss the development and prospects of biomarkers for predicting patient response to ICI treatment in HCC.

Main Methods:

• Review of existing clinical trials and preclinical data on ICI-based combination therapies in HCC.
• Exploration of ongoing studies using transcriptomics and organoid models for biomarker identification.
• Analysis of synergistic mechanisms between anti-PD-1/L1 agents and other targeted therapies (e.g., CTLA-4, VEGF, c-MET).

Main Results:

• Combination strategies involving anti-PD-1/L1 with agents like anti-CTLA-4 or pathway inhibitors show potential synergistic effects.
• These combinations may alter T-cell genomic and functional signatures, alongside immune checkpoint expression.
• Several clinical trials evaluating these combinations are completed or in progress.

Conclusions:

• ICI-based combination therapies represent a promising frontier in advanced HCC treatment, potentially overcoming current limitations.
• The identification of predictive biomarkers is crucial for personalizing ICI treatment strategies and improving patient outcomes in HCC.
• Continued research into combination regimens and biomarker discovery is essential for advancing HCC management.