Objective:

To synthesize how NAFLD-induced lipotoxicity alters the hepatic immune microenvironment and facilitates colorectal cancer liver metastasis.

Approach:

• Immunosuppressive Network: Describes a hierarchical network involving CD4+ T cell apoptosis, Treg expansion, M2 macrophage polarization, and MDSC recruitment.
• Immune Dysregulation: Discusses the link between NAFLD-driven immune dysregulation and reduced responsiveness to immune checkpoint inhibitors.
• Therapeutic Perspectives: Integrates mechanistic insights with potential therapeutic targets for risk stratification and combination immunotherapy.

Key Findings:

• NAFLD is linked to increased frequency and aggressiveness of CRC liver metastases.
• Lipotoxicity from NAFLD reshapes the hepatic immune microenvironment, promoting immunosuppression.
• Expansion of Tregs and CD8+ T cell exhaustion are critical in facilitating CRC metastasis.

Interpretation:

The review discusses the interplay between NAFLD and immune alterations that support colorectal cancer liver metastasis.

Limitations:

• Current evidence linking NAFLD and immune dysregulation to clinical outcomes is limited.
• Need for further validation of findings in clinical settings.

Conclusion:

The findings indicate potential targets for immunotherapy in colorectal cancer patients with NAFLD.