LAUSR

Immune checkpoint inhibitor (ICI) monotherapy yields lower response rates and higher progressive disease (PD) rates than the recently developed combination immunotherapy regimen [1, 2]. Addition of an anti-vascular endothelial growth factor (VEGF) antibody/ tyrosine kinase inhibitor (TKI) to an anti-PD-1/PD-L1 antibody shifts the immunosuppressive tumor microenvironment (TME) to an immune-permissive microenvironment, which may contribute to the positive results of combination therapy. A second contributing factor is that, although ICI monotherapy is ineffective against hepatocellular carcinoma (HCC) with WNT/ β-catenin activating mutations, addition of an anti-VEGF antibody or TKI (which are effective as monotherapy in patients with WNT/β-catenin mutations) should yield a lower PD rate, and consequently a higher response rate. A third factor is that combination therapy might produce synergistic effects by reversing the immunosuppressive TME even in patients with WNT/ β-catenin signaling activation or reduced immunogenicity of another origin. Received: September 14, 2020 Accepted: October 7, 2020 Published online: October 26, 2020