Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma

Area of Science:

• Hepatocellular Carcinoma (HCC) research
• Immunotherapy and Cancer Treatment
• Molecular Signaling in Oncology

Background:

• Advanced hepatocellular carcinoma (HCC) treatment relies on systemic therapy, with targeted therapies offering new molecular insights.
• Despite advances, primary or acquired resistance limits long-term survival and response rates.
• The liver's intrinsic tolerogenic environment and HCC-induced immune tolerance present significant challenges for antitumor immunity.

Purpose of the Study:

• To review the principles of hepatic immunogenic tolerance and immune evasion mechanisms in HCC.
• To elucidate the rationale for immunotherapy in HCC despite the tolerogenic liver environment.
• To critically analyze current literature on immune checkpoint inhibitors (ICIs) in advanced HCC and their combinations.

Main Methods:

• Review of basic principles of hepatic immunogenic tolerance and HCC immune evasion.
• Analysis of biological rationale for immunotherapy in the context of liver cancer.
• Critical evaluation of clinical trial data on ICIs and combinatorial strategies in advanced HCC.

Main Results:

• Immune checkpoint inhibitors (ICIs) demonstrate a promising role in advanced HCC treatment.
• Combinatorial strategies, including ICIs with antiangiogenic agents or multikinase inhibitors, are under active investigation.
• Understanding HCC-induced immune tolerance is crucial for developing effective immunotherapeutic approaches.

Conclusions:

• Immunotherapy, particularly ICIs, offers a promising avenue for advanced HCC, despite the liver's immunosuppressive nature.
• Combinations of ICIs with other agents are being explored to enhance efficacy and overcome resistance.
• Further research into challenges and future directions is essential for optimizing ICI-based treatments in HCC.