EBV‐positive B‐cell lymphomas and lymphoproliferative disorders: Review from the perspective of immune escape and immunodeficiency

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.