Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC

Area of Science:

• Oncology
• Immunology
• Metabolism

Background:

• Immune checkpoint inhibitors (ICIs) are effective against many cancers, including viral hepatocellular carcinoma (HCC).
• Metabolic-associated steatohepatitis-related HCC (MASH-HCC) shows significant resistance to ICIs.
• The metabolic-immune crosstalk mechanisms driving MASH-HCC resistance are not well-defined, and strategies to enhance ICI efficacy are needed.

Purpose of the Study:

• To elucidate the microenvironmental features of MASH-HCC.
• To focus on tumor metabolic-immune crosstalk mechanisms in MASH-HCC.
• To summarize current research on using metabolic drugs to overcome ICI resistance in MASH-HCC.

Main Methods:

• Review of microenvironmental features in MASH-HCC.
• Analysis of metabolic reprogramming, metabolic stress, fibrosis, and the gut-liver axis in MASH-HCC.
• Summary of clinical and preclinical studies on metabolic drugs and ICI efficacy.

Main Results:

• MASH-HCC exhibits unique microenvironmental characteristics contributing to ICI resistance.
• Metabolic reprogramming, stress, fibrosis, and gut-liver axis alterations are key factors in MASH-HCC.
• Emerging evidence suggests metabolic drugs may improve ICI effectiveness.

Conclusions:

• Understanding MASH-HCC's metabolic-immune crosstalk is crucial for improving immunotherapy.
• Metabolic interventions hold promise for enhancing ICI efficacy in MASH-HCC patients.
• Further research is needed to translate these findings into clinical practice.