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

American Journal of Blood Research

Michael Green¹  Jamie P Nourse¹  Ralf Trappe¹  Pauline Crooks¹  Olivier Ramuz¹  Peter Mollee¹  Maher K Gandhi¹  Erica Han¹  Nathan Ross¹  Kimberley Jones¹  Andrew Grigg¹  Lyn Griffith¹  Do Nguyen-Van¹  Colm Keane¹  Frank Vari¹ 

关键词: Epstein-Barr virus;    diffuse large B-cell lymphoma;    EBNA3A;    T-cell;    epitope;    immunotherapy;    posttransplantation lymphoproliferative disorder;   

DOI  :  

学科分类：血液学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown