EBV-Positive Diffuse Large B-Cell Lymphoma (DLBCL): An Assessment and a Roadmap

Diffuse large B-cell Lymphoma (DLBCL) is the most common lymphoma subtype worldwide. The Epstein Barr Virus (EBV) is a human DNA virus associated with a spectrum of human malignancies. EBV is detected in 5% to 15% of DLBCL tumors with no history of immunosuppression. Early reports of EBV-positive DLBCL suggested distinct clinical presentation, unique tumor microenvironment (TME), and inferior survival compared to EBV-negative DLBCL. A better definition of EBV-positive cases treated with modern chemo-immunotherapy has recently improved our understanding of this entity. Recent studies have provided initial insights into the distinct mutational landscape and immune microenvironment of EBV-positive DLBCL and identified EBV as an independent prognostic biomarker in DLBCL. Despite these advances, fundamental questions remain. We provide an overview of emerging clinical and molecular aspects of EBV-positive DLBCL and discuss recent efforts to develop EBV-targeting therapies. We also discuss key research questions in EBV-positive DLBCL.