We produced and analyzed the transcriptomic profiles of 40 lymphoma patients. We used microarrays to compare the global gene expression profile between the different subtypes. These samples were analyzed with a tool predictive of immune escape mechanisms previously developped, IEGS33. Depending on lymphoma subtype, different immune escape signatures can be observed. Therapeutic based on PD-1/PD-L1 blockade shows promising results in Hodgkin lymphoma (HL) and in some diffuse large B-cell lymphoma (DLBCL) patients but biomarkers predicting therapeutic response are still lacking. To gain understanding on the overall immune-escape (IE) mechanism, we recently developed a tool to score the transcriptional IE hallmarks in lymphoma samples and identified four stages of cancer immune-editing in DLBCL that correlated with overall survival. Through this method, we described here the IE profiles in HL and DLBCL from a meta-analysis of large series of microarrays. We observed that HL clustered together at the late equilibrium-early escape stage of cancer immune-editing with significant enrichment of genes involved in IE and T-cell activation as compared to DLBCL. Deconvolution of transcriptomes and immunohistochimistry showed that HL had higher CD3+ and CD4+ T-cells than all DLBCL and shared high abundance of CD8+ T-cells with DLBCL ABC and low infiltrates of CD68+CD163+ macrophages with DLBCL GC. HL and DLBCL shared the same cellular distribution of PD-1 and TIM3 staining but HL exhibited a higher expression of PD-L1 in tumor cells as well as LAG3 overexpression in ME as compared to DLBCL. Finally, our bioinformatic tools based on IEGS33 and T cell activation scores as global approach of immune escape mechanisms help to investigate in details the ME of HL. This method may be useful tool to identify HL as well as DLBCL patients who better benefit from immunotherapy strategies.
Overall design
Frozen biopsies of previously diagnosed lymphomas (B cell lymphomas, Hodgkin lymphomas, T cell lymphomas) were selected for RNA extraction and hybridization on GeneChip® Human Gene HTA_2.0 microarrays.
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