gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

CMV infection in glioblastoma leads to shortened overall survival and TMZ resistance in vitro and in vivo

CMV-Infektion beim Glioblastom führt in vitro und in vivo zu verkürztem Gesamtüberleben und TMZ-Resistenz

Meeting Abstract

  • presenting/speaker Harald Krenzlin - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Elnaz Tabatabaei - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Felix Corr - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Florian Ringel - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Naureen Keric - Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV283

doi: 10.3205/22dgnc274, urn:nbn:de:0183-22dgnc2740

Published: May 25, 2022

© 2022 Krenzlin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: The oncomodulatory human cytomegalovirus (HCMV) is detectable in glioblastoma (GBM) and associated with worse prognosis. The effects of HCMV seropositivity on survival and response to chemotherapy with Temozolomid (TMZ) is largely unknown. We aimed to determine the association between HCMV serostatus at diagnosis, survival and treatment response via a retrospective cohort study of GBM patients.

Methods: 68 patients with glioblastoma (39 male, 29 females; mean age 67.2+-12.27 years) and 10 controls (5 male, 5 females; mean age 60.3+-11.63 years) were included in our study. All patients were treated as inpatients at our department and received adjuvant therapy in our outpatient clinic. Mean follow up was 3 months or until time of death. Polymerase chain reaction was used to detect CMV (PCR). Anti-CMV IgM and IgG were measured using Enzyme linked immunosorbent assays (ELISA). Tumor samples were stained via immunofluorescence using an anti-CMV polyclonal- and anti-pp65 monoclonal antibody. CMV immediate early gene (IE1) and envelope glycoprotein B (gB) mRNA expression in tumor specimen was analyzed using RT-PCR. Absorbance measurement (PrestoBlue) was used to investigate cell viability in response to TMZ in glioblastoma stem cells in vitro.

Results: Anti-CMV IgG were detected in 33 (48,5%) patients and 6 (60%) controls. Anti-CMV IgM was detected in one patient, viral DNA was not detected. CMV IgG antibody levels ranged from levels 1.1 to >250 U/ml (131.1+-84.92 U/mL). CMV antigens were detect in tumor specimen of all seropositive patients and were absent from those that were seronegative. Using RT-PCR, IE1 and gB were only detected in tumors from seropositive patients while it was not detectable in total RNA from normal cerebral cortex of healthy individuals. In our cohort, mean progression free survival (PFS, 187.8+-125.7) and overall survival (OS, 361.9+-212.6 days; p=0.037) was significantly shorter in seropositive glioblastoma patients compared to CMV naïve patients. OS in MGMT methylated patients treated with TMZ was significantly shorter in seropositive patients (p=0.042). Cell viability was higher indicating resistance in HCMV infected GSCs after treatment with TMZ in vitro, compared to uninfected GSCs (p=0.0039)

Conclusion: Our findings ad proof that CMV has an oncomodulatory role in patients with glioblastoma. Seropositivity does correlate with shortened PFS and OS, while infection of glioblastoma stem cells in vitro leads to increased resistance to TMZ.