Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Effici...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-03-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1398877 |
| _version_ | 1818382915524886528 |
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| author | Jeroen F. Vermeulen Wim Van Hecke Elisabeth J. M. Adriaansen Mieke K. Jansen Rianne G. Bouma José Villacorta Hidalgo Paul Fisch Roel Broekhuizen Wim G. M. Spliet Marcel Kool Niels Bovenschen |
| author_facet | Jeroen F. Vermeulen Wim Van Hecke Elisabeth J. M. Adriaansen Mieke K. Jansen Rianne G. Bouma José Villacorta Hidalgo Paul Fisch Roel Broekhuizen Wim G. M. Spliet Marcel Kool Niels Bovenschen |
| author_sort | Jeroen F. Vermeulen |
| collection | DOAJ |
| description | Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas. Cytotoxic T-cells, infiltrating medulloblastomas with variable activation status, showed no correlation with overall survival of the patients. We found limited numbers of PD1+ T-cells and complete absence of PD-L1 on medulloblastomas. Medulloblastomas downregulated immune recognition molecules MHC-I and CD1 d. Intriguingly, expression of granzyme inhibitors SERPINB1 and SERPINB4 was acquired in 23% and 50% of the tumors, respectively. Concluding, pediatric medulloblastomas exploit multiple immune evasion strategies to overcome immune surveillance. Absence of PD-L1 expression in medulloblastoma suggest limited or no added value for immunotherapy with PD1/PD-L1 blockers. |
| first_indexed | 2024-12-14T02:58:03Z |
| format | Article |
| id | doaj.art-422db8e3c8f1429882907bb048bfdc97 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-14T02:58:03Z |
| publishDate | 2018-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-422db8e3c8f1429882907bb048bfdc972022-12-21T23:19:34ZengTaylor & Francis GroupOncoImmunology2162-402X2018-03-017310.1080/2162402X.2017.13988771398877Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastomaJeroen F. Vermeulen0Wim Van Hecke1Elisabeth J. M. Adriaansen2Mieke K. Jansen3Rianne G. Bouma4José Villacorta Hidalgo5Paul Fisch6Roel Broekhuizen7Wim G. M. Spliet8Marcel Kool9Niels Bovenschen10University Medical Center UtrechtUniversity Medical Center UtrechtUniversity Medical Center UtrechtUniversity Medical Center UtrechtUniversity Medical Center UtrechtInstitute of Clinical Pathology, University Medical Center FreiburgInstitute of Clinical Pathology, University Medical Center FreiburgUniversity Medical Center UtrechtUniversity Medical Center UtrechtDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) HeidelbergUniversity Medical Center UtrechtPediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas. Cytotoxic T-cells, infiltrating medulloblastomas with variable activation status, showed no correlation with overall survival of the patients. We found limited numbers of PD1+ T-cells and complete absence of PD-L1 on medulloblastomas. Medulloblastomas downregulated immune recognition molecules MHC-I and CD1 d. Intriguingly, expression of granzyme inhibitors SERPINB1 and SERPINB4 was acquired in 23% and 50% of the tumors, respectively. Concluding, pediatric medulloblastomas exploit multiple immune evasion strategies to overcome immune surveillance. Absence of PD-L1 expression in medulloblastoma suggest limited or no added value for immunotherapy with PD1/PD-L1 blockers.http://dx.doi.org/10.1080/2162402X.2017.1398877medulloblastomabrain cancerpediatricserpinpd-1pd-l1immune evasiontumor-infiltrating lymphocytes |
| spellingShingle | Jeroen F. Vermeulen Wim Van Hecke Elisabeth J. M. Adriaansen Mieke K. Jansen Rianne G. Bouma José Villacorta Hidalgo Paul Fisch Roel Broekhuizen Wim G. M. Spliet Marcel Kool Niels Bovenschen Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma OncoImmunology medulloblastoma brain cancer pediatric serpin pd-1 pd-l1 immune evasion tumor-infiltrating lymphocytes |
| title | Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma |
| title_full | Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma |
| title_fullStr | Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma |
| title_full_unstemmed | Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma |
| title_short | Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma |
| title_sort | prognostic relevance of tumor infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma |
| topic | medulloblastoma brain cancer pediatric serpin pd-1 pd-l1 immune evasion tumor-infiltrating lymphocytes |
| url | http://dx.doi.org/10.1080/2162402X.2017.1398877 |
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