EBV-Positive Lymphomas Associated With Somatic Alterations in Genes Encoding for PD-L1 and PD-L2

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Detection of specific mutations in genes encoding for PD-L1 and PD-L2 may help predict which patients with lymphoma will benefit from immune checkpoint inhibitor therapy.
Detection of specific mutations in genes encoding for PD-L1 and PD-L2 may help predict which patients with lymphoma will benefit from immune checkpoint inhibitor therapy.

Somatic alterations in genes encoding for programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) occur frequently in lymphomas that are associated with prior Epstein-Barr viral infection, according to a study published online on January 24, 2019 in Leukemia.

Infection with the Epstein-Barr virus (EBV), a human gamma-1 herpesvirus, has been linked to a range of lymphoproliferative disorders and malignant lymphomas, including Burkitt lymphoma, EBV-positive T-cell and natural killer (NK)-cell proliferations, and a subset of diffuse B-cell lymphoma (DLBCL). Nevertheless, only a small subset of EBV-infected individuals develop lymphoma, with oncogenesis typically proceeded by a long latency period.

To investigate possible somatic alterations underlying the development of EBV-positive lymphomas, 384 EBV-positive and EBV-negative lymphoma specimens, representing varying histologies, were interrogated using high-throughput targeted DNA sequencing.

Somatic alterations in the genes encoding for PD-L1 and PD-L2 were common in EBV-positive lymphomas (22%), and were observed in extranodal NK/T-cell lymphoma (23%), in aggressive NK-cell leukemia (57%), in systemic EBV-positive T-cell lymphoproliferative disorder (17%), in EBV-positive DLBCL (19%), and in peripheral T-cell lymphoma-not otherwise specified (15%). In contrast, only 5% of EBV-negative lymphomas were characterized by these types of somatic alterations.

These findings may make it possible to “exploit a new diagnostic strategy to identify patients who are likely to respond to PD-1/PD-L1 blockade therapy by detection of EBV and/or PD-L1/PD-L2 genetic alterations in NHLs [non-Hodgkin lymphomas],” the authors concluded.

Reference

  1. Kataoka K, Miyoshi H, Sakata S, et al. Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas [published online January 25, 2019]. Leukemia. doi: 10.1038/s41375-019-0380-5

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