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Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Granai, Massimo; Mundo, Lucia; Akarca, Ayse U.; Siciliano, Maria Chiara; Rizvi, Hasan; Mancini, Virginia; Onyango, Noel; Nyagol, Joshua; Abinya, Nicholas Othieno; Maha, Ibrahim; Margielewska, Sandra; Wi, Wenbin; Bibas, Michele; Piccaluga, Pier Paolo; Quintanilla-Martinez, Leticia; Fend, Falko; Lazzi, Stefano; Leoncini, Lorenzo; Marafioti, Teresa

Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program Thumbnail


Authors

Massimo Granai

Lucia Mundo

Ayse U. Akarca

Maria Chiara Siciliano

Hasan Rizvi

Virginia Mancini

Noel Onyango

Joshua Nyagol

Nicholas Othieno Abinya

Ibrahim Maha

Sandra Margielewska

Wenbin Wi

Michele Bibas

Pier Paolo Piccaluga

Leticia Quintanilla-Martinez

Falko Fend

Stefano Lazzi

Lorenzo Leoncini

Teresa Marafioti



Contributors

Abstract

Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. Methods: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. Results: Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. Conclusion: In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

Citation

Granai, M., Mundo, L., Akarca, A. U., Siciliano, M. C., Rizvi, H., Mancini, V., …Marafioti, T. (2020). Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program. Infectious Agents and Cancer, 15(1), Article 28. https://doi.org/10.1186/s13027-020-00292-w

Journal Article Type Article
Acceptance Date Apr 20, 2020
Online Publication Date May 6, 2020
Publication Date 2020
Deposit Date Jun 3, 2020
Publicly Available Date Mar 29, 2024
Journal Infectious Agents and Cancer
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 15
Issue 1
Article Number 28
DOI https://doi.org/10.1186/s13027-020-00292-w

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Copyright Statement
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons
licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.




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