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The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma
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 are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV(‐neg) DLBCL is well‐established,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899834/ https://www.ncbi.nlm.nih.gov/pubmed/31211907 http://dx.doi.org/10.1111/ejh.13274 |
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author | Keane, Colm Tobin, Joshua Gunawardana, Jay Francis, Santiyagu Gifford, Grace Gabrielli, Sara Gill, Anthony Stevenson, William Talaulikar, Dipti Gould, Clare Jain, Sanjiv Birch, Simone Hertzberg, Mark Gandhi, Maher K. |
author_facet | Keane, Colm Tobin, Joshua Gunawardana, Jay Francis, Santiyagu Gifford, Grace Gabrielli, Sara Gill, Anthony Stevenson, William Talaulikar, Dipti Gould, Clare Jain, Sanjiv Birch, Simone Hertzberg, Mark Gandhi, Maher K. |
author_sort | Keane, Colm |
collection | PubMed |
description | 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 are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV(‐neg) DLBCL is well‐established, it remains untested whether the TME influences survival in EBV(‐pos) DLBCL. There are no data with new digital gene expression technologies that simultaneously interrogate the virus, B cells and the tumour 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% vs 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. |
format | Online Article Text |
id | pubmed-6899834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68998342019-12-19 The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma Keane, Colm Tobin, Joshua Gunawardana, Jay Francis, Santiyagu Gifford, Grace Gabrielli, Sara Gill, Anthony Stevenson, William Talaulikar, Dipti Gould, Clare Jain, Sanjiv Birch, Simone Hertzberg, Mark Gandhi, Maher K. Eur J Haematol Original Articles 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 are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV(‐neg) DLBCL is well‐established, it remains untested whether the TME influences survival in EBV(‐pos) DLBCL. There are no data with new digital gene expression technologies that simultaneously interrogate the virus, B cells and the tumour 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% vs 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. John Wiley and Sons Inc. 2019-07-24 2019-09 /pmc/articles/PMC6899834/ /pubmed/31211907 http://dx.doi.org/10.1111/ejh.13274 Text en © 2019 The Authors European Journal of Haematology Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Keane, Colm Tobin, Joshua Gunawardana, Jay Francis, Santiyagu Gifford, Grace Gabrielli, Sara Gill, Anthony Stevenson, William Talaulikar, Dipti Gould, Clare Jain, Sanjiv Birch, Simone Hertzberg, Mark Gandhi, Maher K. The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma |
title | The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma |
title_full | The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma |
title_fullStr | The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma |
title_full_unstemmed | The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma |
title_short | The tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in EBV‐positive diffuse large B‐cell lymphoma |
title_sort | tumour microenvironment is immuno‐tolerogenic and a principal determinant of patient outcome in ebv‐positive diffuse large b‐cell lymphoma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899834/ https://www.ncbi.nlm.nih.gov/pubmed/31211907 http://dx.doi.org/10.1111/ejh.13274 |
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