Core Viewpoint - The inhibition of ACLY promotes tumor immunity and suppresses liver cancer, particularly in the context of metabolic dysfunction-related fatty liver disease driving hepatocellular carcinoma (MASH-HCC) [3][8]. Group 1: Research Findings - The study published in Nature indicates that inhibiting ACLY can significantly reduce tumor burden in MASH-HCC mouse models by over 70% [6]. - A novel ACLY small molecule inhibitor, EVT0185, was developed, which enhances the efficacy of standard treatment regimens including tyrosine kinase inhibitors and immunotherapy [7]. - The research demonstrated that reduced levels of ACLY in tumors correlate with increased levels of chemokine CXCL13, increased tumor-infiltrating B cells, and the formation of tertiary lymphoid structures [7]. Group 2: Mechanisms of Action - Cancer cells reprogram their metabolic processes to support uncontrolled growth and evade immune surveillance, often through enhanced glycolysis and de novo lipogenesis [5]. - The unique immune-suppressive microenvironment of MASH-HCC poses challenges for immunotherapy, as it is characterized by features such as reduced B cell infiltration and downregulated expression of chemokines [5][6]. - The study suggests that targeting tumor metabolism can reshape immune function and inhibit the carcinogenic process in MASH-HCC [8].