Structural Variations Involving Programmed Death Ligands In B-Cell And T-Cell Lymphomas

Immune checkpoint blockade using anti-PD-1 or anti-PD-L1 antibodies is a highly promising therapy that can induce a durable anti-tumor response and a long-term remission in many patients with multiple cancer types. In particular, the excellent efficacy of anti-PD-1 antibody has been reported in advanced cases with classical Hodgkin lymphoma (cHL), of which high frequency of genetic lesions involving PD-L1 and/or PD-L2 somatic alterations is a defining feature, suggesting a close link between the relevant genetic lesions and the efficacy of anti-PD-1/PD-L1 therapy. In addition to cHL, several subtypes of B-cell lymphomas are shown to have structural variations (SVs) involving PD-1 ligands, such as gene amplification and chromosomal translocation causing promoter replacement. Moreover, recently we reported unique SVs disrupting the 3′-untranslated region (UTR) of PD-L1 in a diversity of cancers, including adult T-cell leukemia/lymphoma (ATL) and diffuse large B-cell lymphoma (DLBCL). However, the comprehensive landscape of PD-L1 and PD-L2 alterations in non-Hodgkin lymphomas has not been fully elucidated. Therefore, in this study, we interrogated PD-L1 and PD-L2 genetic aberrations and characterized their features in a variety of non-Hodgkin lymphomas.