Notably, CD8+ T cell functional heterogeneity has prognostic significance: Notch1 signaling upregulation and exhausted phenotypes (PD-1+TIM-3+LAG-3+) correlate with immunotherapy resistance and poor outcomes[14], whereas the XCL1-positive subset predicts favorable survival in virus-associated HCC[15]. This evidence concerns the gene LAG3 and hepatocellular carcinoma.