Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program

Massimo Granai
,
Lucia Mundo
,
Ayse U. Akarca
,
Maria Chiara Siciliano
,
Hasan Rizvi
,
Ester Sorrentino
,
Virginia Mancini
,
Maha Ibrahim
,
Sandra Margielewska
,
Wenbin Wei
,
Michele Bibas
,
Noel Onyango
,
Joshua Nyagol
,
Pier Paolo Piccaluga
ORCID logo ,
Leticia Quintanilla-Martinez
ORCID logo ,
Falko Fend
,
Stefano Lazzi
,
Lorenzo Leoncini
* ,
Teresa Marafioti
*
Version 1 : Received: 16 January 2020 / Approved: 18 January 2020 / Online: 18 January 2020 (09:01:45 CET)

How to cite: Granai, M.; Mundo, L.; Akarca, A.U.; Siciliano, M.C.; Rizvi, H.; Sorrentino, E.; Mancini, V.; Ibrahim, M.; Margielewska, S.; Wei, W.; Bibas, M.; Onyango, N.; Nyagol, J.; Piccaluga, P.P.; Quintanilla-Martinez, L.; Fend, F.; Lazzi, S.; Leoncini, L.; Marafioti, T. Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program. Preprints 2020, 2020010195. https://doi.org/10.20944/preprints202001.0195.v1 Granai, M.; Mundo, L.; Akarca, A.U.; Siciliano, M.C.; Rizvi, H.; Sorrentino, E.; Mancini, V.; Ibrahim, M.; Margielewska, S.; Wei, W.; Bibas, M.; Onyango, N.; Nyagol, J.; Piccaluga, P.P.; Quintanilla-Martinez, L.; Fend, F.; Lazzi, S.; Leoncini, L.; Marafioti, T. Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program. Preprints 2020, 2020010195. https://doi.org/10.20944/preprints202001.0195.v1

Abstract

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. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated 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. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

Keywords

Burkitt's lymphoma; Epstein-Barr Virus

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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