Journal
CANCERS
Volume 10, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/cancers10110415
Keywords
lymphoma; immune escape; Hodgkin's lymphoma; immune checkpoints; TIM-3; datamining
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Universite Toulouse III: Paul Sabatier
- Centre National de la Recherche Scientifique (CNRS)
- Laboratoire d'Excellence Toulouse Cancer (TOUCAN) [ANR11-LABX]
- Programme Hospitalo-Universitaire en Cancerologie CAPTOR [ANR11-PHUC0001]
- ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Sante, National Alliance for Life Sciences Health)
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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 similar to 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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