Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme
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)...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-07-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418302214 |
| _version_ | 1811208684979617792 |
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| author | Liu Zhenjiang Martin Rao Xiaohua Luo Davide Valentini Anna von Landenberg Qingda Meng Georges Sinclair Nina Hoffmann Julia Karbach Hans-Michael Altmannsberger Elke Jäger Inti Harvey Peredo Ernest Dodoo Markus Maeurer |
| author_facet | Liu Zhenjiang Martin Rao Xiaohua Luo Davide Valentini Anna von Landenberg Qingda Meng Georges Sinclair Nina Hoffmann Julia Karbach Hans-Michael Altmannsberger Elke Jäger Inti Harvey Peredo Ernest Dodoo Markus Maeurer |
| author_sort | Liu Zhenjiang |
| collection | DOAJ |
| description | 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-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. 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 survivin97–111 peptide (p = .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 (p = .024), and the combined presence of serum IFN-γ/TNF-α/IL-17a (p = .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. Keywords: Glioblastoma multiforme, Cytokine networks, Survivin, Immune response, Survival benefit, Immunotherapy |
| first_indexed | 2024-04-12T04:26:49Z |
| format | Article |
| id | doaj.art-7b086ad50e594d07afcf83e382f6d956 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-12T04:26:49Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-7b086ad50e594d07afcf83e382f6d9562022-12-22T03:48:04ZengElsevierEBioMedicine2352-39642018-07-01334956Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma MultiformeLiu Zhenjiang0Martin Rao1Xiaohua Luo2Davide Valentini3Anna von Landenberg4Qingda Meng5Georges Sinclair6Nina Hoffmann7Julia Karbach8Hans-Michael Altmannsberger9Elke Jäger10Inti Harvey Peredo11Ernest Dodoo12Markus Maeurer13Division of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for allogeneic stem cell transplantation (CAST), Karolinska University Hospital, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology and Haematology, Krankenhaus Nordwest, Frankfurt/Main, GermanyInstitute of Pathology, Krankenhaus Nordwest, Frankfurt/Main, GermanyDepartment of Oncology and Haematology, Krankenhaus Nordwest, Frankfurt/Main, GermanyDepartment of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, SwedenDivision of Therapeutic Immunology (TIM), Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for allogeneic stem cell transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden; Corresponding author at: Krankenhaus Nordwest, Dept of Oncology/Hematology, Frankfurt/Main, Germany and Champalimaud Foundation, Lisbon, Portugal.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-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. 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 survivin97–111 peptide (p = .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 (p = .024), and the combined presence of serum IFN-γ/TNF-α/IL-17a (p = .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. Keywords: Glioblastoma multiforme, Cytokine networks, Survivin, Immune response, Survival benefit, Immunotherapyhttp://www.sciencedirect.com/science/article/pii/S2352396418302214 |
| spellingShingle | Liu Zhenjiang Martin Rao Xiaohua Luo Davide Valentini Anna von Landenberg Qingda Meng Georges Sinclair Nina Hoffmann Julia Karbach Hans-Michael Altmannsberger Elke Jäger Inti Harvey Peredo Ernest Dodoo Markus Maeurer Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme EBioMedicine |
| title | Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme |
| title_full | Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme |
| title_fullStr | Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme |
| title_full_unstemmed | Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme |
| title_short | Cytokine Networks and Survivin Peptide-Specific Cellular Immune Responses Predict Improved Survival in Patients With Glioblastoma Multiforme |
| title_sort | cytokine networks and survivin peptide specific cellular immune responses predict improved survival in patients with glioblastoma multiforme |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418302214 |
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