Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme.
EBioMedicine
; 33: 49-56, 2018 Jul.
Article
en En
| MEDLINE
| ID: mdl-30049387
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). PATIENTS ANDMETHODS:
Peripheral blood from 205 treatment-naïve patients with glioma (GBMâ¯=â¯145; non-GBMâ¯=â¯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 1000â¯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.RESULTS:
Approximately 2% of patients with GBM and 18% of patients with non-GBM glioma, were alive beyond 1000â¯days of surgery. Univariate analysis indicated that the combination of three cytokines (IL-4/IL-5/IL-6, pâ¯=â¯.0022; IFN-γ/TNF-α/IL-17A, pâ¯=â¯.0083) but not a 'partial' combination of these cytokines, the IFN-γ immune response to EBV-EBNA-1 (pâ¯<â¯.0001) as well as T-cell responses to the survivin97-111 peptide (pâ¯=â¯.0152) correlated with longer survival among patients with GBM. Multivariate analysis identified survivin97-111-directed IFN-γ production with IL-2/IL-15/IL-21 conditioning (pâ¯=â¯.024), and the combined presence of serum IFN-γ/TNF-α/IL-17a (pâ¯=â¯.003) as independent predictors of survival.CONCLUSION:
Serum cytokine patterns and lymphocyte reactivity to survivin97-111, 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Citocinas
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Glioblastoma
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Proteínas Inhibidoras de la Apoptosis
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
EBioMedicine
Año:
2018
Tipo del documento:
Article
País de afiliación:
Suecia