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Eur J Haematol. 2019 Jun 18. doi: 10.1111/ejh.13274. [Epub ahead of print]

The tumor microenvironment is immuno-tolerogenic and a principal determinant of patient outcome in EBV positive Diffuse Large B Cell Lymphoma.

Author information

1
Mater Research, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
2
Princess Alexandra Hospital, Brisbane, QLD, Australia.
3
Kolling Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
4
Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.
5
NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia, 2065.
6
Canberra Hospital, ACT, Australia.
7
Australia National University Medical School, ACT, Australia.
8
Pathology Queensland, Brisbane, QLD, Australia.
9
Prince of Wales Hospital, Sydney, NSW, Australia.

Abstract

OBJECTIVE:

Epstein-Barr virus positive Diffuse Large B-Cell Lymphoma (EBV-pos DLBCL) is a recently identified entity. Data regarding outcome to frontline immuno-chemotherapy is conflicting. Although the prognostic impact of the tumor microenvironment (TME) in EBV-neg DLBCL is well-established, it remains untested whether the TME influences survival in EBV-pos DLBCL. There is no data with new digital gene expression technologies that simultaneously interrogate the virus, B-cells and the tumor microenvironment (TME).

METHODS:

We used the NanoString platform in a population-based cohort of 433 patients to establish if the technology could detect EBV in the tumour biopsies and to investigate the influence that EBV has on the complex tumour microenvironment of DLBCL.

RESULTS:

Incidence of EBV-pos DLBCL was 6.9% with 5-year survival of 65% versus 82% in EBV-neg DLBCL (p=0.018). EBV-pos tissues had similar expression of T-cell genes compared to EBV-neg DLBCL but higher levels of the antigen-presenting molecule B2M. This was countered by elevated PD-L1, PD-L2, LAG3 and TIM3 immune-checkpoints and a higher CD163/CD68 'M2' macrophage score.

CONCLUSION:

In EBV-pos DLBCL the TME is immuno-tolerogenic and may explain the poor outcomes seen in this subtype of DLBCL. This article is protected by copyright. All rights reserved.

KEYWORDS:

DLBCL ; EBV ; Immune Checkpoints; Tumour Associated Macrophages; Tumour Microenvironment

PMID:
31211907
DOI:
10.1111/ejh.13274

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