Immunotherapy such as immune checkpoint inhibitors holds great promise for advanced HCC; however, recent data suggested that patients with NAFLD-associated HCC are less sensitive to conventional immune checkpoint inhibition due to the altered immune components.16-18 Studies have reported that the activation of intrahepatic CD8+T cells promotes the NASH-to-HCC transition.19,20 Pfister et al7 revealed that aberrantly activated CD8+PD1+ T cells in the TME involve in NASH-induced liver injury and progression of NASH to HCC, which may limit the response to immunotherapy. The gene discussed is CD8A; the disease is metabolic dysfunction-associated steatohepatitis.