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Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme.
- Source :
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EBioMedicine [EBioMedicine] 2018 Jul; Vol. 33, pp. 49-56. Date of Electronic Publication: 2018 Jun 29. - Publication Year :
- 2018
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Abstract
- Purpose: We investigated serum cytokine and T-cell responses directed against tumour-associated antigens (TAAs) in association with survival of patients with glioblastoma multiforme (GBM).<br />Patients and Methods: Peripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A). Patients were followed-up for at least 1000 days post-surgery. Survivin protein and gene expression in resected GBM tumour tissue were confirmed by immunohistochemistry and real-time polymerase chain reaction, respectively. Antigen-specific T-cell responses were gauged by ICS (intracellular cytokine production). Associations between patient survival and immunological reactivity patterns were analysed using univariate and multivariate statistics.<br />Results: Approximately 2% of patients with GBM and 18% of patients with non-GBM glioma, were alive beyond 1000 days of surgery. Univariate analysis indicated that the combination of three cytokines (IL-4/IL-5/IL-6, p = .0022; IFN-γ/TNF-α/IL-17A, p = .0083) but not a 'partial' combination of these cytokines, the IFN-γ immune response to EBV-EBNA-1 (p < .0001) as well as T-cell responses to the survivin <subscript>97-111</subscript> peptide (p = .0152) correlated with longer survival among patients with GBM. Multivariate analysis identified survivin <subscript>97-111</subscript> -directed IFN-γ production with IL-2/IL-15/IL-21 conditioning (p = .024), and the combined presence of serum IFN-γ/TNF-α/IL-17a (p = .003) as independent predictors of survival.<br />Conclusion: Serum cytokine patterns and lymphocyte reactivity to survivin <subscript>97-111</subscript> , particularly with IL-2, IL-15 and IL-21 conditioning may be instrumental in predicting survival among patients with GBM. This has implications for clinical follow-up of patients with GBM and the targeted development of immunotherapy for patients with CNS tumours.<br /> (Copyright © 2018. Published by Elsevier B.V.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Brain Neoplasms blood
Brain Neoplasms genetics
Brain Neoplasms immunology
Female
Glioblastoma blood
Glioblastoma genetics
Glioblastoma immunology
Humans
Male
Middle Aged
Neoplasm Grading
Survival Analysis
Survivin
Young Adult
Brain Neoplasms surgery
Cytokines blood
Glioblastoma surgery
Inhibitor of Apoptosis Proteins genetics
Inhibitor of Apoptosis Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 33
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 30049387
- Full Text :
- https://doi.org/10.1016/j.ebiom.2018.06.014