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

伯基特淋巴瘤的免疫景观揭示了 M2 巨噬细胞极化以及 PD-L1 表达与非典型 EBV 潜伏期程序之间的相关性

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作者: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, Lor

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.

Conclusion

In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

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.

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