Persistent exposure to TSAs promotes the exhaustion of CD8+ T cells, which characteristically expressed high levels of PD-1 and CD39.465,466 The intratumoral CD8+ T cells with high PD-1 expression show an intrinsically high capacity for tumor recognition.468 Given the potent activation of CD39+CD8+ T cells by high-affinity neoantigens, patients with hepatocellular carcinoma in high-affinity neoantigens-high group benefited more from anti-PD-1 therapy than high-affinity neoantigen-low group.123. The gene discussed is CD8A; the disease is neoplasm.