Moreover, TIM-3 was significantly up-regulated in NK in HCC, and inhibited its cytokine production and cytotoxic activity by inhibiting phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR)1 signaling pathway, leading to dysfunction of NK cells in hepatocellular carcinoma (HCC) [45]. This evidence concerns the gene HAVCR2 and hepatocellular carcinoma.