Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme.

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 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-?, IFN-? 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. 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-?/TNF-?/IL-17A, p?=?.0083) but not a 'partial' combination of these cytokines, the IFN-? immune response to EBV-EBNA-1 (p?

SUBMITTER: Zhenjiang L 

PROVIDER: S-EPMC6085502 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature