Cancers, Vol. 10, Pages 415: Profiling Immune Escape in Hodgkin’s and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining

Cancers, Vol. 10, Pages 415: Profiling Immune Escape in Hodgkin's and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining

Cancers doi: 10.3390/cancers10110415

Authors: Sarah Péricart Marie Tosolini Pauline Gravelle Cédric Rossi Alexandra Traverse-Glehen Nadia Amara Camille Franchet Elodie Martin Christine Bezombes Guy Laurent Pierre Brousset Jean-Jacques Fournié Camille Laurent

Therapeutic blockade of PD-1/PD-L1 shows promising results in Hodgkin’s lymphoma (HL) and in some diffuse large B-cell lymphoma (DLBCL) patients, but biomarkers predicting such responses are still lacking. To this end, we recently developed a transcriptional scoring of immune escape (IE) in cancer biopsies. Using this method in DLBCL, we identified four stages of IE correlated with overall survival, but whether Hodgkin’s lymphomas (HL) also display this partition was unknown. Thus, we explored the transcriptomic profiles of ~1000 HL and DLBCL using a comparative meta-analysis of their bulk microarrays. Relative to DLBCL, the HL co-clustered at the advanced stage of immune escape, displaying significant enrichment of both IE and T-cell activation genes. Analyses via transcriptome deconvolution and immunohistochemistry showed more CD3+ and CD4+ tumor-infiltrating lymphocytes (TILs) in HL than DLBCL. Both HL and non-GCB DLBCL shared a high abundance of infiltrating CD8+ T-cells, but HL had less CD68+CD163+ macrophages. The same cellular distribution of PD-1 and TIM-3 was observed in HL and DLBCL, though HL had more PD-L1 tumor cells and LAG-3 ME cells. This study illuminates the advanced stage of immune activation and escape in HL, consistent with the response to checkpoint blockade therapies for this type of lymphoma.

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