Please use this identifier to cite or link to this item:
Title: Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response
Authors: Marrão, Gina 
Habib, Mohammed
Paiva, Artur 
Bicout, Dominique
Fallecker, Catherine
Franco, Sofia 
Fafi-Kremer, Samira
Simões da Silva, Teresa
Morand, Patrice
Freire-de-Oliveira, Carlos 
Drouet, Emmanuel
Keywords: Breast cancer; EBV; Viral load; Tumor; Immunocompetent cells; IFN-γ, TNF-α; Survival; Multivariate analysis; ZEBRA
Issue Date: 11-Sep-2014
Publisher: Springer Nature
Project: “Fonds Unique Interministériel” of FUI-DGE DiagEBV 
Serial title, monograph or event: BMC Cancer
Volume: 14
Issue: 1
Abstract: Background: For nearly two decades now, various studies have reported detecting the Epstein-Barr virus (EBV) in breast cancer (BC) cases. Yet the results are unconvincing, and their interpretation has remained a matter of debate. We have now presented prospective data on the effect of EBV infection combined with survival in patients enrolled in a prospective study. Methods: We assessed 85 BC patients over an 87-month follow-up period to determine whether EBV infection, evaluated by qPCR in both peripheral blood mononuclear cells (PBMCs) and tumor biopsies, interacted with host cell components that modulate the evolution parameters of BC. We also examined the EBV replicating form by the titration of serum anti-ZEBRA antibodies. Immunological studies were performed on a series of 35 patients randomly selected from the second half of the survey, involving IFN-γ and TNF-α intracellular immunostaining tests performed via flow cytometry analysis in peripheral NK and T cells, in parallel with EBV signature. The effect of the EBV load in the blood or tumor tissue on patient survival was analyzed using univariate and multivariate analyses, combined with an analysis of covariance. Results: Our study represents the first ever report of the impact of EBV on the clinical outcome of BC patients, regardless of tumor histology or treatment regimen. No correlation was found between: (i) EBV detection in tumor or PBMCs and tumor characteristics; (ii) EBV and other prognostic factors. Notably, patients exhibiting anti-ZEBRA antibodies at high titers experienced poorer overall survival (p = 0.002). Those who recovered from their disease were found to have a measurable EBV DNA load, together with a high frequency of IFN-γ and TNF-α producing PBMCs (p = 0.04), which indicates the existence of a Th1-type polarized immune response in both the tumor and its surrounding tissue. Conclusions: The replicative form of EBV, as investigated using anti-ZEBRA titers, correlated with poorer outcomes, whereas the latent form of the virus that was measured and quantified using the EBV tumor DNA conferred a survival advantage to BC patients, which could occur through the activation of non-specific anti-tumoral immune responses.
ISSN: 1471-2407
DOI: 10.1186/1471-2407-14-665
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

Show full item record

Page view(s)

checked on May 22, 2024


checked on May 22, 2024

Google ScholarTM




This item is licensed under a Creative Commons License Creative Commons