Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program
Open Access
- 6 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Infectious Agents and Cancer
- Vol. 15 (1), 1-8
- https://doi.org/10.1186/s13027-020-00292-w
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 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. 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. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.Other Versions
This publication has 53 references indexed in Scilit:
- PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated MalignanciesClinical Cancer Research, 2013
- Clinical significance of CD163+ tumor‐associated macrophages in patients with adult T‐cell leukemia/lymphomaCancer Science, 2013
- The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell InfectionPLOS ONE, 2013
- Treatment of Burkitt lymphoma in equatorial Africa using a simple three‐drug combination followed by a salvage regimen for patients with persistent or recurrent diseaseBritish Journal of Haematology, 2012
- Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypesBlood, 2011
- Tumor-Associated Macrophages and Survival in Classic Hodgkin's LymphomaThe New England Journal of Medicine, 2010
- Burkitt Lymphoma: Pathogenesis and Immune EvasionJournal of Oncology, 2010
- Human herpesvirus 8 (HHV-8) inhibits monocyte differentiation into dendritic cells and impairs their immunostimulatory activityImmunology Letters, 2007
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapiesThe Journal of Pathology, 2002