The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma
Immunotherapies with immune checkpoint inhibitors or adoptive cell transfer have become powerful tools to treat cancer. These treatments act via overcoming or alleviating tumor-induced immunosuppression, thereby enabling effective tumor clearance. Glioblastoma (GBM) represents the most aggressive, p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/9/2292 |
| _version_ | 1827663222765780992 |
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| author | Mitrajit Ghosh Anna M. Lenkiewicz Bozena Kaminska |
| author_facet | Mitrajit Ghosh Anna M. Lenkiewicz Bozena Kaminska |
| author_sort | Mitrajit Ghosh |
| collection | DOAJ |
| description | Immunotherapies with immune checkpoint inhibitors or adoptive cell transfer have become powerful tools to treat cancer. These treatments act via overcoming or alleviating tumor-induced immunosuppression, thereby enabling effective tumor clearance. Glioblastoma (GBM) represents the most aggressive, primary brain tumor that remains refractory to the benefits of immunotherapy. The immunosuppressive immune tumor microenvironment (TME), genetic and cellular heterogeneity, and disorganized vasculature hinder drug delivery and block effector immune cell trafficking and activation, consequently rendering immunotherapy ineffective. Within the TME, the mutual interactions between tumor, immune and endothelial cells result in the generation of positive feedback loops, which intensify immunosuppression and support tumor progression. We focus here on the role of aberrant tumor vasculature and how it can mediate hypoxia and immunosuppression. We discuss how immune cells use immunosuppressive signaling for tumor progression and contribute to the development of resistance to immunotherapy. Finally, we assess how a positive feedback loop between vascular normalization and immune cells, including myeloid cells, could be targeted by combinatorial therapies with immune checkpoint blockers and sensitize the tumor to immunotherapy. |
| first_indexed | 2024-03-10T00:38:51Z |
| format | Article |
| id | doaj.art-f6f1e4c11fac4982bbed6b4d0edf4193 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:38:51Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-f6f1e4c11fac4982bbed6b4d0edf41932023-11-23T15:12:20ZengMDPI AGBiomedicines2227-90592022-09-01109229210.3390/biomedicines10092292The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of GlioblastomaMitrajit Ghosh0Anna M. Lenkiewicz1Bozena Kaminska2Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandImmunotherapies with immune checkpoint inhibitors or adoptive cell transfer have become powerful tools to treat cancer. These treatments act via overcoming or alleviating tumor-induced immunosuppression, thereby enabling effective tumor clearance. Glioblastoma (GBM) represents the most aggressive, primary brain tumor that remains refractory to the benefits of immunotherapy. The immunosuppressive immune tumor microenvironment (TME), genetic and cellular heterogeneity, and disorganized vasculature hinder drug delivery and block effector immune cell trafficking and activation, consequently rendering immunotherapy ineffective. Within the TME, the mutual interactions between tumor, immune and endothelial cells result in the generation of positive feedback loops, which intensify immunosuppression and support tumor progression. We focus here on the role of aberrant tumor vasculature and how it can mediate hypoxia and immunosuppression. We discuss how immune cells use immunosuppressive signaling for tumor progression and contribute to the development of resistance to immunotherapy. Finally, we assess how a positive feedback loop between vascular normalization and immune cells, including myeloid cells, could be targeted by combinatorial therapies with immune checkpoint blockers and sensitize the tumor to immunotherapy.https://www.mdpi.com/2227-9059/10/9/2292tumor vasculatureimmune suppressionvascular normalizationglioblastomaimmunotherapyimmune checkpoint blockade |
| spellingShingle | Mitrajit Ghosh Anna M. Lenkiewicz Bozena Kaminska The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma Biomedicines tumor vasculature immune suppression vascular normalization glioblastoma immunotherapy immune checkpoint blockade |
| title | The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma |
| title_full | The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma |
| title_fullStr | The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma |
| title_full_unstemmed | The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma |
| title_short | The Interplay of Tumor Vessels and Immune Cells Affects Immunotherapy of Glioblastoma |
| title_sort | interplay of tumor vessels and immune cells affects immunotherapy of glioblastoma |
| topic | tumor vasculature immune suppression vascular normalization glioblastoma immunotherapy immune checkpoint blockade |
| url | https://www.mdpi.com/2227-9059/10/9/2292 |
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