Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: clinical features and survival impact

M COHEN ; A VISTAROP; F HUAMAN ; M NARBAITZ; F METREBIAN; E DE MATTEO; M V PRECIADO; P CHABAY

Scientific Reports

Nature Publishing Group

Año: 2017

2045-2322

Epstein?Barr Virus (EBV) is present in the neoplastic cells of around 15% of patients with diffuse large B-cell lymphoma (DLBCL) from Asian and Latin-American populations. Even though a tolerogenic microenvironment was recently described in DLBCL cases, little is known concerning the immunomodulatory features induced by EBV presence in tumor cells. Previous reports have suggested that, in patients who develop Hodgkin lymphoma, EBV-specific subsets of circulating cytotoxic T-cells are increased but they are dysfunctional, showing signs of immune exhaustion. Hence, suppression of host immunity is assumed to play a critical role in tumor progression. This study aimed to investigate, in a wide age-range cohort of DLBCL patients, whether an association between certain features of tumor microenvironment and EBV presence is taking place. Cytokine and chemokine transcripts expression and immunophenotype analysis of both EBV+ and EBV- tumors showed that EBV infection increased gene microenvironment expression of immunosuppressive cytokine (IL-10), with a trend to peritumoral distribution of the IL-10+ cells. Hallmarks of augmented CD8+T-cell population and cytotoxic effector cells related marker granzyme B were also displayed. However, this specific immune response might be impaired by the tolerogenic milieu, characterized by PD-1 expression, which prevailed in both EBV+ and EBV- DLBCL cases. Our results lead to a better understanding of the interplay between lymphoma cells and their microenvironment in a viral framework. They could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.