title: Enhanced neutrophil activity is associated with shorter time to tumor progression in glioblastoma patients.
abstract: Glioblastoma multiforme (GBM) is a highly malignant tumor with a poor outcome that is often positive for human cytomegalovirus (HCMV). GBM patients often have excessive numbers of neutrophils and macrophages near and within the tumor. Here, we characterized the cytokine patterns in the blood of GBM patients with and without Valganciclovir treatment. Furthermore, we determined whether neutrophil activation is related to HCMV status and patient outcome. Blood samples for analyses of cytokines and growth factors were collected from 42 GBM patients at the time of diagnosis (n = 42) and at weeks 12 and 24 after surgery. Blood neutrophils of 28 GBM patients were examined for CD11b expression. The levels of pro- and anti-inflammatory cytokines and chemokines-including interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, transforming growth factor (TGF)-β1, interferon-γ, interferon-α, tumor necrosis factor α, and monocyte chemoattractant protein (MCP)-1were analyzed with a bead-based flow cytometry assay. During the first six months after surgery, neutrophil activity was increased in 12 patients and was unchanged or decreased in 16. Patients with increased neutrophil activity had enhanced IL-12p70, high grade HCMV and a shorter time to tumor progression (TTP) than patients without or decreased neutrophil activity (median TTP; 5.4 vs. 12 months, 95% confidence interval; 1.6-10 vs. 0.1-0.6, hazard ratio = 3 vs. 0.4,p= 0.004). The levels of IL-12p70 were significantly decreased in Valganciclovir treated patients (n = 22, T 12W vs. T 24W,p= 0.03). In conclusion, our findings suggest that neutrophil activation is an early sign of tumor progression in GBM patients.
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Cederarv
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Wolmer-Solberg
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Tammik
authors.affiliation: Department of Neurology, Karolinska University Hospital, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Stragliotto
authors.affiliation: Department of Neurology, Karolinska University Hospital, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Inti
authors.initials: I
authors.lastname: Peredo
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Olesja
authors.initials: O
authors.lastname: Fornara
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Xinling
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Mensur
authors.initials: M
authors.lastname: Dzabic
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Chato
authors.initials: C
authors.lastname: Taher
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Skarman
authors.affiliation: Department of Medicine Solna, Microbial Pathogenesis Research Unit, Center for Molecular Medicine, Karolinska Institute , Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Nauclér
keywords: Cytokines; glioblastoma multiforme; human cytomegalovirus; neutrophils; time to tumor progression; valganciclovir