TME constitutes the principle mechanism of immunoresistance, which can be overcome by multiple therapeutic strategies, such as the utilization of (i) angiogenesis inhibitors, that could possibly promote the anti-tumor response to ICIs, while an ongoing study in phase I/II, demonstrates anti-PD1 agent, pembrolizumab, combined with VEGFR inhibitor, lenvatinib for end-stage HCC [79]. This evidence concerns the gene PDCD1 and neoplasm.