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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

Epstein–Barr virus- and cytomegalovirus-specific immune response in patients with brain cancer

Authors: Zhenjiang Liu, Thomas Poiret, Qingda Meng, Martin Rao, Anna von Landenberg, Esther Schoutrop, Davide Valentini, Ernest Dodoo, Inti Peredo-Harvey, Markus Maeurer

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

Background

Patients with brain tumor or pancreatic cancer exhibit the poorest prognosis, while immune fitness and cellular immune exhaustion impacts their survival immensely. This work identifies differences in the immune reactivity to the common human pathogens cytomegalovirus (CMV) and Epstein–Barr virus (EBV) between patients with brain tumor in comparison to those with pancreatic cancer and healthy individuals.

Methods

We characterized the humoral and cellular immune responses of patients with brain tumor or pancreatic cancer to cytomegalovirus structural protein pp65 (CMV-pp65) as well as Epstein–Barr nuclear antigen-1 (EBNA-1) by whole-blood assay and ELISA.

Results

Anti-CMV-pp65 plasma immunoglobulin gamma (IgG) titers were significantly lower in patients with brain tumor compared to healthy donors and patients with pancreatic cancer. Among the responding patients with GBM, those with a weak anti-CMV IgG response also had a decreased median overall survival (p = 0.017, 667 vs 419 days) while patients with brain tumor showed a generally suppressed anti-CMV immune-reactivity. Patients with brain tumor exhibited a significantly lower interferon gamma (IFNγ) response to EBNA-1 and CMV-pp65 compared to patients with pancreatic cancer or healthy donors. This antigen-specific response was further amplified in patients with brain tumor upon conditioning of whole blood with IL-2/IL-15/IL-21. Exclusively in this setting, among the responding patients with GBM, those exhibiting a EBV-specific cellular immune response above the median also displayed an increased median overall survival pattern compared to weak responders (753 vs 370 days, p < 0.001).

Conclusions

This report provides (i) a fast and easy assay using common viral antigens and cytokine stimulation to screen for immune fitness/exhaustion of patients with brain tumor in comparison to pancreatic cancer and healthy individuals and (ii) EBV/CMV-induced IFNγ production as a potential marker of survival in patients with brain tumor.
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Metadata
Title
Epstein–Barr virus- and cytomegalovirus-specific immune response in patients with brain cancer
Authors
Zhenjiang Liu
Thomas Poiret
Qingda Meng
Martin Rao
Anna von Landenberg
Esther Schoutrop
Davide Valentini
Ernest Dodoo
Inti Peredo-Harvey
Markus Maeurer
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1557-9

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