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, 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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number28
Pages (from-to)1-8
Number of pages8
JournalInfectious Agents and Cancer
Volume15
Issue number1
DOIs
Publication statusPublished - May 6 2020

Keywords

  • Burkitt lymphoma
  • EBV
  • Immune checkpoint
  • Immunotherapy
  • PD-L1
  • Tumour microenvironment

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Infectious Diseases
  • Cancer Research

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    Granai, M., Mundo, L., Akarca, A. U., Siciliano, M. C., Rizvi, H., Mancini, V., Onyango, N., Nyagol, J., Abinya, N. O., Maha, I., Margielewska, S., Wi, W., Bibas, M., Piccaluga, P. P., Quintanilla-Martinez, L., Fend, F., Lazzi, S., Leoncini, L., & 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), 1-8. [28]. https://doi.org/10.1186/s13027-020-00292-w