Hot and Cold HCC: Uncoupling Viral Oncogenesis and Therapy

Area of Science:

• Oncology
• Immunology
• Hepatology

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern, ranking as the sixth most common cancer and third leading cause of cancer mortality.
• Hepatitis B and C virus infections are significant risk factors for HCC, contributing to its carcinogenicity through direct and indirect mechanisms, including immune exhaustion.
• Persistent immune system alterations in HCC patients, even after viral suppression, can impede treatment response.

Purpose of the Study:

• To review the epidemiology and prevention strategies for HCC.
• To explore the distinct tumor microenvironments of "hot" and "cold" HCC.
• To summarize mechanisms for converting cold HCC tumors to hot and discuss combination checkpoint inhibitor therapy.

Main Methods:

• Literature review of HCC epidemiology and prevention.
• Analysis of "hot" and "cold" tumor microenvironment models in HCC.
• Synthesis of research on mechanisms for cold-to-hot tumor conversion.
• Review of evidence for combination checkpoint inhibitor therapy in HCC.

Main Results:

• HCC incidence and mortality rates are increasing worldwide.
• Tumor microenvironments in HCC can be classified as "hot" or "cold," influencing immunotherapy response.
• Strategies to convert "cold" HCC tumors to "hot" may enhance immunotherapy efficacy.

Conclusions:

• Prevention through Hepatitis B vaccination and viral hepatitis treatment is crucial for HCC.
• Understanding and manipulating tumor microenvironments is key to improving HCC immunotherapy.
• Combination checkpoint inhibitor therapy shows promise for HCC treatment, particularly in "hot" tumors.