[Genetic Alterations Involving PD-L1/PD-L2 in Human Malignancies]

Although immune checkpoint blockade therapy using anti-PD-1/PD-L1 antibodies can induce durable remission in a variety of human malignancies, the mechanisms regulating the expression of PD-1 ligands(PD-L1 and PD-L2)have not been fully investigated. Recently, we newly identified structural variations(SVs)disrupting the 3'-untranslated region(UTR)of the PD- L1/PD-L2 genes in various cancers, which caused a marked upregulation of these molecules and mediated immune escape of tumor cells. Particularly, these alterations were frequently observed in virus-related lymphomas, such as adult T-cell leukemia/ lymphoma as well as Epstein-Barr virus-positive diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma. These results suggest a pivotal role of PD-L1/PD-L2-mediated immune evasion in the pathogenesis of virus-related tumors. Here we summarize the genetic alterations involving the PD-L1/PD-L2 genes in human cancers, highlighting their relevance in virusassociated tumors.