Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8 T-cell epitopes

• Published in: American journal of blood research Vol. 1; no. 2; pp. 146 - 159
• Main Authors: Nguyen-Van, Do, Keane, Colm, Han, Erica, Jones, Kimberley, Nourse, Jamie P, Vari, Frank, Ross, Nathan, Crooks, Pauline, Ramuz, Olivier, Green, Michael, Griffith, Lyn, Trappe, Ralf, Grigg, Andrew, Mollee, Peter, Gandhi, Maher K
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2011
• Subjects: Original; T-cell; immunotherapy; EBNA3A; Epstein-Barr virus; diffuse large B-cell lymphoma; epitope; posttransplantation lymphoproliferative disorder
• ISSN: 2160-1992

Post-transplantation lymphoproliferative disorders (PTLD) arise in the immunosuppressed and are frequently Epstein-Barr virus (EBV) associated. The most common PTLD histological sub-type is diffuse large B-cell lymphoma (EBV+DLBCL-PTLD). Restoration of EBV-specific T-cell immunity can induce EBV+DLBCL-PTLD regression. The most frequent B-cell lymphoma in the immunocompetent is also DLBCL. 'EBV-positive DLBCL of the elderly' (EBV+DLBCL) is a rare but well-recognized DLBCL entity that occurs in the overtly immunocompetent, that has an adverse outcome relative to EBV-negative DLBCL. Unlike PTLD (which is classified as viral latency III), literature suggests EBV+DLBCL is typically latency II, i.e. expression is limited to the immuno-subdominant EBNA1, LMP1 and LMP2 EBV-proteins. If correct, this would be a major impediment for T-cell immunotherapeutic strategies. Unexpectedly we observed EBV+DLBCL-PTLD and EBV+DLBCL both shared features consistent with type III EBV-latency, including expression of the immuno-dominant EBNA3A protein. Extensive analysis showed frequent polymorphisms in EB-NA1 and LMP1 functionally defined CD8+ T-cell epitope encoding regions, whereas EBNA3A polymorphisms were very rare making this an attractive immunotherapy target. As with EBV+DLBCL-PTLD, the antigen presenting machinery within lymphomatous nodes was intact. EBV+DLBCL express EBNA3A suggesting it is amenable to immunotherapeutic strategies.