Immune microenvironment and immunotherapy strategies in MAFLD-related hepatocellular carcinoma

Abstract

Driven by the global pandemic of obesity and metabolic syndrome, metabolic-associated fatty liver disease (MAFLD) has emerged as a principal driver of hepatocellular carcinoma (HCC). MAFLD-related HCC (MAFLD-HCC) exhibits distinct pathological features and a unique immune microenvironment, which collectively contribute to its poorer response to immune checkpoint inhibitors (ICIs) compared to HCC of other etiologies. This review systematically outlines the immune microenvironment in MAFLD-HCC, focusing on the dynamic changes and interactions among dysfunctional CD8⁺ T cells, regulatory T cells, myeloid cells, and B cells, as well as their crosstalk with metabolic reprogramming. These changes collectively result in a highly immunosuppressive tumor microenvironment, leading to resistance to ICIs. Addressing the challenges in treating MAFLD-HCC, this paper discusses the current progress in immunotherapy for MAFLD-HCC and explores potential directions for future immunotherapy research.

Keywords

MAFLD-related HCC / immune microenvironment / immunotherapy

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