Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives
Glioblastomas are aggressive, fast-growing primary brain tumors. After standard-of-care treatment with radiation in combination with temozolomide, the overall prognosis of newly diagnosed patients remains poor, with a 2-year survival rate of less than 20%. The remarkable survival benefit gained with...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/3/751 |
| _version_ | 1797765667033710592 |
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| author | Bas Weenink Pim J. French Peter A.E. Sillevis Smitt Reno Debets Marjolein Geurts |
| author_facet | Bas Weenink Pim J. French Peter A.E. Sillevis Smitt Reno Debets Marjolein Geurts |
| author_sort | Bas Weenink |
| collection | DOAJ |
| description | Glioblastomas are aggressive, fast-growing primary brain tumors. After standard-of-care treatment with radiation in combination with temozolomide, the overall prognosis of newly diagnosed patients remains poor, with a 2-year survival rate of less than 20%. The remarkable survival benefit gained with immunotherapy in several extracranial tumor types spurred a variety of experimental intervention studies in glioblastoma patients. These ranged from immune checkpoint inhibition to vaccinations and adoptive T cell therapies. Unfortunately, almost all clinical outcomes were universally disappointing. In this perspective, we provide an overview of immune interventions performed to date in glioblastoma patients and re-evaluate their performance. We argue that shortcomings of current immune therapies in glioblastoma are related to three major determinants of resistance, namely: low immunogenicity; immune privilege of the central nervous system; and immunosuppressive micro-environment. In this perspective, we propose strategies that are guided by exact shortcomings to sensitize glioblastoma prior to treatment with therapies that enhance numbers and/or activation state of CD8 T cells. |
| first_indexed | 2024-03-12T20:13:23Z |
| format | Article |
| id | doaj.art-2bfd579207e74d99a18101dcd8687897 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:13:23Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2bfd579207e74d99a18101dcd86878972023-08-02T01:28:16ZengMDPI AGCancers2072-66942020-03-0112375110.3390/cancers12030751cancers12030751Immunotherapy in Glioblastoma: Current Shortcomings and Future PerspectivesBas Weenink0Pim J. French1Peter A.E. Sillevis Smitt2Reno Debets3Marjolein Geurts4Department of Neurology, Erasmus MC Cancer Institute, Be430A, PO Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Neurology, Erasmus MC Cancer Institute, Be430A, PO Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Neurology, Erasmus MC Cancer Institute, Be430A, PO Box 2040, 3000 CA Rotterdam, The NetherlandsLaboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, 3000 CA Rotterdam, The NetherlandsDepartment of Neurology, Erasmus MC Cancer Institute, Be430A, PO Box 2040, 3000 CA Rotterdam, The NetherlandsGlioblastomas are aggressive, fast-growing primary brain tumors. After standard-of-care treatment with radiation in combination with temozolomide, the overall prognosis of newly diagnosed patients remains poor, with a 2-year survival rate of less than 20%. The remarkable survival benefit gained with immunotherapy in several extracranial tumor types spurred a variety of experimental intervention studies in glioblastoma patients. These ranged from immune checkpoint inhibition to vaccinations and adoptive T cell therapies. Unfortunately, almost all clinical outcomes were universally disappointing. In this perspective, we provide an overview of immune interventions performed to date in glioblastoma patients and re-evaluate their performance. We argue that shortcomings of current immune therapies in glioblastoma are related to three major determinants of resistance, namely: low immunogenicity; immune privilege of the central nervous system; and immunosuppressive micro-environment. In this perspective, we propose strategies that are guided by exact shortcomings to sensitize glioblastoma prior to treatment with therapies that enhance numbers and/or activation state of CD8 T cells.https://www.mdpi.com/2072-6694/12/3/751adoptive t cell therapyantigenscheckpoint inhibitorsclinical studiesglioblastomaimmune privilegetumor micro-environmentvaccines |
| spellingShingle | Bas Weenink Pim J. French Peter A.E. Sillevis Smitt Reno Debets Marjolein Geurts Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives Cancers adoptive t cell therapy antigens checkpoint inhibitors clinical studies glioblastoma immune privilege tumor micro-environment vaccines |
| title | Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives |
| title_full | Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives |
| title_fullStr | Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives |
| title_full_unstemmed | Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives |
| title_short | Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives |
| title_sort | immunotherapy in glioblastoma current shortcomings and future perspectives |
| topic | adoptive t cell therapy antigens checkpoint inhibitors clinical studies glioblastoma immune privilege tumor micro-environment vaccines |
| url | https://www.mdpi.com/2072-6694/12/3/751 |
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