[Novel mechanism of immune evasion in cancer via structural variations of the PD-L1 gene].

Cancer cells are thought to circumvent immune surveillance through PD-1/PD-L1 signaling. However, the genetic basis for PD-L1-PD-L1-mediated immune escape has not been completely understood, with the exception of elevated PD-L1 expression by gene amplification and the utilization of an ectopic promoter by translocation. Recently, we demonstrated a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3' part of the PD-L1 gene. These SVs invariably cause a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3'-untranslated region (UTR), and thereby widely affect multiple common cancer types, including adult T-cell leukemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and adenocarcinoma of the stomach (2%). All SVs invariably result in a prominent increase of aberrant PD-L1 transcripts commonly lacking an intact 3'-UTR, which most typically generate gene fusions with ectopic sequences including integrated viral genomes. In this review, the critical role of 3'-UTR disruption is briefly summarized.