Apart from the contribution of senescent activated HSCs to lowering the risk of HCC, NrasG12V-induced senescent hepatocytes, as pre-malignant cells, can also account for the prevention of HCC occurrence by triggering RAS-specific Th1 CD4+ T cells to activate macrophages to perform immune clearance of OIS hepatocytes [34]. This evidence concerns the gene CD4 and hepatocellular carcinoma.