Inhibiting the JAK1/STAT1 signaling pathway by knocking out TRIM65 polarizes tumor‐associated macrophages to the M1‐like phenotype, thus inhibiting the development of HCC [83], while gut microbiota‐derived d‐lactate reprograms M2‐like tumor‐associated macrophages toward an M1‐like phenotype via PI3Kδ‐dependent lactate sensing, enhancing the ability of Kupffer cells to clear pathogens and reshape the immunosuppressive TME in HCC mice [82]. The gene discussed is TRIM65; the disease is hepatocellular carcinoma.