Epstein-Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma

Aisling M Ross; Ciara I Leahy; Fiona Neylon; Jana Steigerova; Patrik Flodr; Martina Navratilova; Helena Urbankova; Katerina Vrzalikova; Lucia Mundo; Stefano Lazzi; Lorenzo Leoncini; Matthew Pugh; Paul G Murray

doi:10.3390/life13020521

Epstein-Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma

Aisling M Ross, Ciara I Leahy, Fiona Neylon, Jana Steigerova, Patrik Flodr, Martina Navratilova, Helena Urbankova, Katerina Vrzalikova, Lucia Mundo, Stefano Lazzi, Lorenzo Leoncini, Matthew Pugh^*, Paul G Murray^*

^*Corresponding author for this work

Immunology and Immunotherapy

Research output: Contribution to journal › Review article › peer-review

Abstract

Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances. We then explore the recent reclassification of EBV+ DLBCL as an established entity in the WHO fifth edition and ICC 2022 classifications, emphasising the unique nature of this entity. To that end, we also explore the unique genetic background of this entity and briefly discuss the potential role of the tumour microenvironment in lymphomagenesis and disease progression. Despite the recent progress in elucidating the mechanisms of this malignancy, much work remains to be done to improve patient stratification, treatment strategies, and outcomes.

Original language	English
Article number	521
Number of pages	18
Journal	Life
Volume	13
Issue number	2
DOIs	https://doi.org/10.3390/life13020521
Publication status	Published - 14 Feb 2023

Bibliographical note

Funding:
We acknowledge financial support from Blood Cancer UK and the Cancer Research UK Birmingham Centre, University of Birmingham, Birmingham, United Kingdom. The work was also supported by a European Regional Development Fund Project (ENOCH: CZ.02.1.01/0.0/0.0/16_019/0000868) and by the Marie Skłodowska-Curie Actions grant funding at the University of Limerick (VirGO 896422).

Keywords

Epstein–Barr virus
diffuse large B-cell lymphoma
tumour microenvironment
chronic inflammation

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Cite this

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title = "Epstein-Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma",

abstract = "Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances. We then explore the recent reclassification of EBV+ DLBCL as an established entity in the WHO fifth edition and ICC 2022 classifications, emphasising the unique nature of this entity. To that end, we also explore the unique genetic background of this entity and briefly discuss the potential role of the tumour microenvironment in lymphomagenesis and disease progression. Despite the recent progress in elucidating the mechanisms of this malignancy, much work remains to be done to improve patient stratification, treatment strategies, and outcomes.",

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author = "Ross, {Aisling M} and Leahy, {Ciara I} and Fiona Neylon and Jana Steigerova and Patrik Flodr and Martina Navratilova and Helena Urbankova and Katerina Vrzalikova and Lucia Mundo and Stefano Lazzi and Lorenzo Leoncini and Matthew Pugh and Murray, {Paul G}",

note = "Funding: We acknowledge financial support from Blood Cancer UK and the Cancer Research UK Birmingham Centre, University of Birmingham, Birmingham, United Kingdom. The work was also supported by a European Regional Development Fund Project (ENOCH: CZ.02.1.01/0.0/0.0/16_019/0000868) and by the Marie Sk{\l}odowska-Curie Actions grant funding at the University of Limerick (VirGO 896422).",

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AU - Ross, Aisling M

AU - Leahy, Ciara I

AU - Neylon, Fiona

AU - Steigerova, Jana

AU - Flodr, Patrik

AU - Navratilova, Martina

AU - Urbankova, Helena

AU - Vrzalikova, Katerina

AU - Mundo, Lucia

AU - Lazzi, Stefano

AU - Leoncini, Lorenzo

AU - Pugh, Matthew

AU - Murray, Paul G

N1 - Funding: We acknowledge financial support from Blood Cancer UK and the Cancer Research UK Birmingham Centre, University of Birmingham, Birmingham, United Kingdom. The work was also supported by a European Regional Development Fund Project (ENOCH: CZ.02.1.01/0.0/0.0/16_019/0000868) and by the Marie Skłodowska-Curie Actions grant funding at the University of Limerick (VirGO 896422).

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N2 - Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances. We then explore the recent reclassification of EBV+ DLBCL as an established entity in the WHO fifth edition and ICC 2022 classifications, emphasising the unique nature of this entity. To that end, we also explore the unique genetic background of this entity and briefly discuss the potential role of the tumour microenvironment in lymphomagenesis and disease progression. Despite the recent progress in elucidating the mechanisms of this malignancy, much work remains to be done to improve patient stratification, treatment strategies, and outcomes.

AB - Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances. We then explore the recent reclassification of EBV+ DLBCL as an established entity in the WHO fifth edition and ICC 2022 classifications, emphasising the unique nature of this entity. To that end, we also explore the unique genetic background of this entity and briefly discuss the potential role of the tumour microenvironment in lymphomagenesis and disease progression. Despite the recent progress in elucidating the mechanisms of this malignancy, much work remains to be done to improve patient stratification, treatment strategies, and outcomes.

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KW - tumour microenvironment

KW - chronic inflammation

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DO - 10.3390/life13020521

M3 - Review article

C2 - 36836878

SN - 2075-1729

VL - 13

JO - Life

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IS - 2

M1 - 521

ER -

Epstein-Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma

Abstract

Bibliographical note

Keywords

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