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

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.