Studies suggest a distinctive pro-tumorigenic adaptive immune response in non-viral HCC, characterized by CXCR6+CD8+ T cells with low FOXO1 expression triggering auto-aggression in response to metabolic stimuli in NASH.581,582 Therefore, understanding the unique contributions of different HCC causes in shaping the tumor microenvironment is crucial for identifying potential mechanisms that could be targeted for effective immunotherapy strategies (Fig. 5). The gene discussed is CD8A; the disease is metabolic dysfunction-associated steatohepatitis.