Tumor microenvironment of Dark zone lymphomas

The TME plays a pivotal role in regulating the biology of GC B-cell lymphoma and immune escape strategies. Although there have been numerous studies investigating Lymphoma Microenvironment (LME) in B-cell lymphomas, the extent to which these TME differences reflect the stage of GC differentiation from which B cell lymphoma may originate remains poorly understood. Here we aim to compare the LME in 8 HGBCL-11q, 8 BL EBV-, 5 BL EBV+, 4 HGBCL-BCL2r/MYCr and 5 DLBCL-GCB, EBV-. GEP was performed using the NanoString PanCancer Immune Profiling Panel on FFPE samples and validated by multiplex immunohistochemistry. A PCA showed that HGBCL-11q, BL-EBV- and HGBCL-BCL2r/MYCr grouped together as compared to BL EBV+ and DLBCL-GCB, based on ANOVA analysis of 365 DEGs(p<0.05). To further analyse our cohort, we applied a newly identified DZ\LZ spatial signature (201 LZ and 169-DZ genes). Supervised clustering analysis of the differentially expressed genes revealed that DZ genes were enriched in BL EBV-, HGBCL-11q and HGBCL BCL2r/MYCr. While LZ genes were enriched in DLBCL-GCB and to a lesser extent in BL EBV+. Based on LZ\DZ-spatial signature, our results suggest that BL EBV positive and BL EBV- may originate from different steps of GC reaction. Further analyses aim at determining whether GEP differences are more related to the TME or to the lymphoma cells.