Contrary to the MYC-driven MCD diet NAFLD–HCC mouse model, Dominik Pfister et al. used a CD–HFD-induced NASH mouse model to show that, compared to prophylactic treatment involving anti-PD-1, which was able to increase CD–HFD-induced NASH–HCC transition with a greater number of tumor nodules and greater tumor size, a combination of anti-PD1 and anti-CD4 significantly decreased the number of HCC tumor nodules and the tumor size. Here, MYC is linked to metabolic dysfunction-associated steatohepatitis.