The tumor-intrinsic expression of PD-L1 is aberrantly regulated in many cancers, and the underlying mechanisms include genomic alterations, for example, gene copy number amplification, dysregulated transcription, and 3′-UTR disruption;2 constitutive oncogenic signaling activation (e.g., the loss of PTEN expression); and consequent activation of the PI3K/AKT pathway, activation of the RAS/MAPK pathway, inhibition of p53 signaling, and upregulation of OCT42,50. The gene discussed is PTEN; the disease is cancer.