DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis
Abstract Gliomas, the most frequent type of primary tumor of the central nervous system in adults, results in significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. There...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05514-0 |
| _version_ | 1797977178481098752 |
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| author | Maria Vedunova Victoria Turubanova Olga Vershinina Maria Savyuk Iuliia Efimova Tatiana Mishchenko Robrecht Raedt Anne Vral Christian Vanhove Daria Korsakova Claus Bachert Frauke Coppieters Patrizia Agostinis Abhishek D. Garg Mikhail Ivanchenko Olga Krysko Dmitri V. Krysko |
| author_facet | Maria Vedunova Victoria Turubanova Olga Vershinina Maria Savyuk Iuliia Efimova Tatiana Mishchenko Robrecht Raedt Anne Vral Christian Vanhove Daria Korsakova Claus Bachert Frauke Coppieters Patrizia Agostinis Abhishek D. Garg Mikhail Ivanchenko Olga Krysko Dmitri V. Krysko |
| author_sort | Maria Vedunova |
| collection | DOAJ |
| description | Abstract Gliomas, the most frequent type of primary tumor of the central nervous system in adults, results in significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells, generate long-term memory, and result in significant clinical benefits. This work aimed to investigate the efficacy and molecular mechanism of dendritic cell (DC) vaccines loaded with glioma cells undergoing immunogenic cell death (ICD) induced by photosens-based photodynamic therapy (PS-PDT) and to identify reliable prognostic gene signatures for predicting the overall survival of patients. Analysis of the transcriptional program of the ICD-based DC vaccine led to the identification of robust induction of Th17 signature when used as a vaccine. These DCs demonstrate retinoic acid receptor-related orphan receptor-γt dependent efficacy in an orthotopic mouse model. Moreover, comparative analysis of the transcriptome program of the ICD-based DC vaccine with transcriptome data from the TCGA-LGG dataset identified a four-gene signature (CFH, GALNT3, SMC4, VAV3) associated with overall survival of glioma patients. This model was validated on overall survival of CGGA-LGG, TCGA-GBM, and CGGA-GBM datasets to determine whether it has a similar prognostic value. To that end, the sensitivity and specificity of the prognostic model for predicting overall survival were evaluated by calculating the area under the curve of the time-dependent receiver operating characteristic curve. The values of area under the curve for TCGA-LGG, CGGA-LGG, TCGA-GBM, and CGGA-GBM for predicting five-year survival rates were, respectively, 0.75, 0.73, 0.9, and 0.69. These data open attractive prospects for improving glioma therapy by employing ICD and PS-PDT-based DC vaccines to induce Th17 immunity and to use this prognostic model to predict the overall survival of glioma patients. |
| first_indexed | 2024-04-11T05:03:52Z |
| format | Article |
| id | doaj.art-229b8aa3d4d949289dbd38fbfc39ad30 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T05:03:52Z |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-229b8aa3d4d949289dbd38fbfc39ad302022-12-25T12:31:52ZengNature Publishing GroupCell Death and Disease2041-48892022-12-01131211910.1038/s41419-022-05514-0DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosisMaria Vedunova0Victoria Turubanova1Olga Vershinina2Maria Savyuk3Iuliia Efimova4Tatiana Mishchenko5Robrecht Raedt6Anne Vral7Christian Vanhove8Daria Korsakova9Claus Bachert10Frauke Coppieters11Patrizia Agostinis12Abhishek D. Garg13Mikhail Ivanchenko14Olga Krysko15Dmitri V. Krysko16Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny NovgorodInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny NovgorodInstitute of Information Technology, Mathematics and Mechanics, National Research Lobachevsky State University of Nizhny NovgorodInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny NovgorodCell Death Investigation and Therapy (CDIT) Laboratory, Department of Human Structure and Repair, Ghent UniversityInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod4Brain Team, Department of Head and Skin, Ghent UniversityRadiobiology Research Group, Department of Human Structure and Repair, Ghent UniversityIBiTech-MEDISIP-Infinity Laboratory, Department of Electronics and Information Systems, Ghent UniversityInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny NovgorodUpper Airways Research Laboratory, Department of Head and Skin, Ghent UniversityCenter for Medical Genetics Ghent (CMGG), Department of Biomolecular Medicine, Ghent UniversityLaboratory of Cell Death Research & Therapy, Department of Cellular and Molecular Medicine, KU LeuvenLaboratory of Cell Stress & Immunity (CSI), Department of Cellular & Molecular Medicine, KU LeuvenInstitute of Information Technology, Mathematics and Mechanics, National Research Lobachevsky State University of Nizhny NovgorodCell Death Investigation and Therapy (CDIT) Laboratory, Department of Human Structure and Repair, Ghent UniversityInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny NovgorodAbstract Gliomas, the most frequent type of primary tumor of the central nervous system in adults, results in significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells, generate long-term memory, and result in significant clinical benefits. This work aimed to investigate the efficacy and molecular mechanism of dendritic cell (DC) vaccines loaded with glioma cells undergoing immunogenic cell death (ICD) induced by photosens-based photodynamic therapy (PS-PDT) and to identify reliable prognostic gene signatures for predicting the overall survival of patients. Analysis of the transcriptional program of the ICD-based DC vaccine led to the identification of robust induction of Th17 signature when used as a vaccine. These DCs demonstrate retinoic acid receptor-related orphan receptor-γt dependent efficacy in an orthotopic mouse model. Moreover, comparative analysis of the transcriptome program of the ICD-based DC vaccine with transcriptome data from the TCGA-LGG dataset identified a four-gene signature (CFH, GALNT3, SMC4, VAV3) associated with overall survival of glioma patients. This model was validated on overall survival of CGGA-LGG, TCGA-GBM, and CGGA-GBM datasets to determine whether it has a similar prognostic value. To that end, the sensitivity and specificity of the prognostic model for predicting overall survival were evaluated by calculating the area under the curve of the time-dependent receiver operating characteristic curve. The values of area under the curve for TCGA-LGG, CGGA-LGG, TCGA-GBM, and CGGA-GBM for predicting five-year survival rates were, respectively, 0.75, 0.73, 0.9, and 0.69. These data open attractive prospects for improving glioma therapy by employing ICD and PS-PDT-based DC vaccines to induce Th17 immunity and to use this prognostic model to predict the overall survival of glioma patients.https://doi.org/10.1038/s41419-022-05514-0 |
| spellingShingle | Maria Vedunova Victoria Turubanova Olga Vershinina Maria Savyuk Iuliia Efimova Tatiana Mishchenko Robrecht Raedt Anne Vral Christian Vanhove Daria Korsakova Claus Bachert Frauke Coppieters Patrizia Agostinis Abhishek D. Garg Mikhail Ivanchenko Olga Krysko Dmitri V. Krysko DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis Cell Death and Disease |
| title | DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis |
| title_full | DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis |
| title_fullStr | DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis |
| title_full_unstemmed | DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis |
| title_short | DC vaccines loaded with glioma cells killed by photodynamic therapy induce Th17 anti-tumor immunity and provide a four-gene signature for glioma prognosis |
| title_sort | dc vaccines loaded with glioma cells killed by photodynamic therapy induce th17 anti tumor immunity and provide a four gene signature for glioma prognosis |
| url | https://doi.org/10.1038/s41419-022-05514-0 |
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