Am J Blood Res 2011;1(2):146-159
Original Article
Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly
expresses EBNA3A with conserved CD8+ T-cell epitopes
Do Nguyen-Van, Colm Keane, Erica Han, Kimberley Jones, Jamie P. Nourse, Frank Vari, Nathan Ross, Pauline Crooks,
Olivier Ramuz, Michael Green, Lyn Griffith, Ralf Trappe, Andrew Grigg, Peter Mollee, Maher K. Gandhi
Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane; Department of Haematology,
Princess Alexandra Hospital, Brisbane, Queensland, Australia; Department of Immunopathophysiology, Hanoi Medical
University, Hanoi, Vietnam; Department of Anatomical Pathology, Pathology Queensland, Royal Brisbane and Women's
Hospital, Brisbane, Queensland, Australia; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA,
United States; Genomics Research Centre, School of Medical Sciences, Griffith University, Queensland, Australia; Department
of Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Department of Internal Medicine II,
Kiel, Germany; 8Department of Clinical Haematology, Austin Hospital, Melbourne, Victoria, Australia.
Received July 17, 2011; accepted August 8, 2011; Epub September 9, 2011; published September 30, 2011
Abstract: 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 EBNA1 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 expresses
EBNA3A suggesting it is amenable to immunotherapeutic strategies. (AJBR1107002).
Keywords: Epstein-Barr virus, Diffuse Large B-cell Lymphoma, EBNA3A, T-cell, Epitope, Immunotherapy, Post-transplantation
lymphoproliferative disorder
Full Text PDF
Address all correspondence to:
Dr. Maher K Gandhi
Level I/CBCRC,
Queensland Institute of Medical Research
Herston Road, Brisbane, Queensland, 4006
Australia
Tel: +617 3845 3792
Fax: +617 3845 3510
Email: Maher.Gandhi@qimr.edu.au
Original Article
Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly
expresses EBNA3A with conserved CD8+ T-cell epitopes
Do Nguyen-Van, Colm Keane, Erica Han, Kimberley Jones, Jamie P. Nourse, Frank Vari, Nathan Ross, Pauline Crooks,
Olivier Ramuz, Michael Green, Lyn Griffith, Ralf Trappe, Andrew Grigg, Peter Mollee, Maher K. Gandhi
Clinical Immunohaematology Laboratory, Queensland Institute of Medical Research, Brisbane; Department of Haematology,
Princess Alexandra Hospital, Brisbane, Queensland, Australia; Department of Immunopathophysiology, Hanoi Medical
University, Hanoi, Vietnam; Department of Anatomical Pathology, Pathology Queensland, Royal Brisbane and Women's
Hospital, Brisbane, Queensland, Australia; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA,
United States; Genomics Research Centre, School of Medical Sciences, Griffith University, Queensland, Australia; Department
of Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Department of Internal Medicine II,
Kiel, Germany; 8Department of Clinical Haematology, Austin Hospital, Melbourne, Victoria, Australia.
Received July 17, 2011; accepted August 8, 2011; Epub September 9, 2011; published September 30, 2011
Abstract: 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 EBNA1 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 expresses
EBNA3A suggesting it is amenable to immunotherapeutic strategies. (AJBR1107002).
Keywords: Epstein-Barr virus, Diffuse Large B-cell Lymphoma, EBNA3A, T-cell, Epitope, Immunotherapy, Post-transplantation
lymphoproliferative disorder
Full Text PDF
Address all correspondence to:
Dr. Maher K Gandhi
Level I/CBCRC,
Queensland Institute of Medical Research
Herston Road, Brisbane, Queensland, 4006
Australia
Tel: +617 3845 3792
Fax: +617 3845 3510
Email: Maher.Gandhi@qimr.edu.au
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