Interestingly, it has been demonstrated that in vitro PD-1 blockade upregulates TIGIT expression on NY-ESO-1-reactive CD8+ T cells from melanoma patients (54), and that TIGIT is the most-upregulated immune checkpoint on CD8+ TILs upon anti-PD-1 treatment in a PD-1 non-responsive HCC mouse model (37), suggesting TIGIT as a plausible target to improve efficacy of anti-PD-1 treatment. This evidence concerns the gene CD8A and hepatocellular carcinoma.