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Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients.

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Laurent C, Fabiani B, Do C, Tchernonog E, Cartron G, Gravelle P, Amara N, Malot S, Palisoc M, Copie-Bergman C, Traverse-Glehen A, Copin MC, Brousset P, Pittaluga S, Jaffe ES, Coppo P,


Laurent C, Fabiani B, Do C, Tchernonog E, Cartron G, Gravelle P, Amara N, Malot S, Palisoc M, Copie-Bergman C, Traverse-Glehen A, Copin MC, Brousset P, Pittaluga S, Jaffe ES, Coppo P, (click to view)

Laurent C, Fabiani B, Do C, Tchernonog E, Cartron G, Gravelle P, Amara N, Malot S, Palisoc M, Copie-Bergman C, Traverse-Glehen A, Copin MC, Brousset P, Pittaluga S, Jaffe ES, Coppo P,

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Haematologica 2016 5 12() pii

Abstract

Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma commonly associated with Epstein-Barr virus co-infection that most often occurs in the context of human immunodeficiency virus infection. Therefore, its immune escape strategy may involve the up-regulation of immune-checkpoint proteins allowing the tumor immune evasion. However, the expression of these molecules was poorly studied in this lymphoma. We have investigated 82 plasmablastic lymphoma cases of whom half were Epstein-Barr virus positive. Although they harbored similar pathological features, Epstein-Barr virus positive plasmablastic lymphomas showed a significant increase in MYC gene rearrangement and had a better two-years event-free survival than Epstein-Barr virus negative cases (p=0.049). Immunostains for programmed cell death-1, programmed cell death-ligand 1, indole 2,3-dioxygenase and dendritic cell specific C-type lectin showed a high or moderate expression by the microenvironment cells in 60% to 72% of cases, whereas CD163 was expressed in almost all cases. Tumor cells also expressed programmed cell death-1 and its ligand in 22.5% and 5% of cases, respectively. Both Epstein-Barr virus positive and negative plasmablastic lymphomas exhibited a high immune-checkpoint score showing that it involves several pathways of immune escape. However, Epstein-Barr virus positive lymphomas exhibited a higher expression of programmed cell death-1 and its ligand in both malignant cells and microenvironment as compared to Epstein-Barr virus negative cases. In conclusion, plasmablastic lymphoma expresses immune-checkpoint proteins through both malignant cells and the tumor microenvironment. The expression of programmed cell death-1 and its ligand constitutes a strong rationale for testing monoclonal antibodies in this often chemoresistant disease.

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