Figure 2. Immunosurveillance of senescent hepatocytes by CD4⁺ T cells and T_H1 cytokines. Aberrant oncogene activation in hepatocytes as well as other oncogenic events can induce a state of cellular stress from which hepatocytes can develop tumors, die via apoptosis or undergo cell senescence. CD4⁺ T cells can sense cellular senescence and initiate an immune response that stimulates macrophages to clear senescent cells. Moreover, T_H1 cytokines such as interferon γ (IFNγ) and tumor necrosis factor α (TNFα) promote the senescence of cancer cells. These mechanisms appear important for the suppression of hepatocarcinogenesis.^31,32,33