Notably, hypoxia-mediated HIF-1α increases PD-L1 expression in a variety of solid hypoxic tumors via the PTEN/PI3K/AKT signaling pathway, thereby inducing T-cell unresponsiveness or apoptosis [29], which suggests that the PTEN/PI3K/AKT/HIF axes may be an essential part of the occurrence and development of drug resistance mechanisms in hypoxic HCC. This evidence concerns the gene AKT1 and hepatocellular carcinoma.