Background: Epstein-Barr virus (EBV) is detected in a variety of B-cell lymphomas (BCLs) and B-cell lymphoproliferative disorders (B-LPDs). Immunodeficiency has been considered to play a key role in the pathogenesis of these diseases. In addition, immune escape of tumor cells may also contribute to the development of EBV+ BCLs and B-LPDs. The PD-1/PD-L1 pathway is particularly important for immune escape of tumor cells that contribute to development of lymphoma through suppression of cytotoxic T-cell function. We now consider PD-L1 immunohistochemistry (IHC) a very useful method for predicting whether tumor cells of lymphoid malignancies are characterized by the immune escape mechanism.
Methods: We reviewed articles of EBV+ BCLs and B-LPDs from the perspective of immune escape and immunodeficiency, particularly focusing on PD-L1 IHC.
Results: Based on PD-L1 IHC, we consider that EBV+ BCL and B-LPD can be classified into three types: "immunodeficiency", "immune escape", and "immunodeficiency + immune escape" type. The immunodeficiency type includes EBV+ diffuse large BCL (DLBCL) of the elderly, EBV+ sporadic Burkitt lymphoma, EBV+ mucocutaneous ulcer, and methotrexate (MTX)-associated B-LPD. The immune escape type includes EBV+ classic Hodgkin lymphoma (CHL) and EBV+ DLBCL of the young. The immunodeficiency + immune escape type includes CHL type MTX-associated LPD and a minor subset of EBV+ DLBCL of the elderly.
Conclusions: Recently, good results have been reported for immune check-point inhibitors in treating lymphoma. Lymphomas and LPDs characterized by immune escape are regarded as good candidates for PD1/PD-L1 blockade therapy. Therefore, from both the clinical and pathological perspective, we suggest that lymphoma diagnosis should be made considering immune escape and immunodeficiency.
Keywords: EBV-positive lymphoma; PD-L1; immune escape; immunodeficiency; lymphoproliferative disorder.
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.