EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity
Medulloblastoma (MB) is a pediatric brain tumor that develops in the cerebellum, representing one of the most common malignant brain cancers in children. Standard treatments include surgery, chemotherapy, and radiation, but despite a 5-y survival rate of approximately 70%, these therapies often lead...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2485535 |
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| author | Lola Boutin Mingzhi Liu Julie Déchanet Merville Oscar Bedoya-Reina Margareta T Wilhelm |
| author_facet | Lola Boutin Mingzhi Liu Julie Déchanet Merville Oscar Bedoya-Reina Margareta T Wilhelm |
| author_sort | Lola Boutin |
| collection | DOAJ |
| description | Medulloblastoma (MB) is a pediatric brain tumor that develops in the cerebellum, representing one of the most common malignant brain cancers in children. Standard treatments include surgery, chemotherapy, and radiation, but despite a 5-y survival rate of approximately 70%, these therapies often lead to significant neurological damage in the developing brain. This underscores the urgent need for less toxic, more effective therapeutic alternatives. Recent advancements in cancer immunotherapy, including immune checkpoint inhibitors and CAR-T cell therapy, have revolutionized cancer treatment. One promising avenue is the use of Gamma Delta (γδ)T cells, a unique T cell population with potential advantages, such as non-alloreactivity, potent tumor cell lysis, and broad antigen recognition. However, their capacity to recognize and target MB cells remains underexplored. To investigate the therapeutic potential of γδT cells against MB, we analyzed the proportion and status of MB-infiltrated γδT cells within patient datasets. We next investigated the expression of γδT cell ligands on MB cells and identified the EphA2 receptor and the phosphoantigen/Butyrophilin complex as key ligands, activating Vγ9 Vδ1 and Vγ9 Vδ2 T cells, respectively, leading to significant MB cell lysis in both monolayer and spheroid models. Importantly, preliminary safety data showed that γδT cells did not target differentiated neurons or neuroepithelial stem cells derived from induced pluripotent stem cells, underscoring the selectivity and safety of this approach. In conclusion, γδT cells trigger an efficient and specific killing of MB and would offer a promising novel therapeutic strategy. |
| format | Article |
| id | doaj-art-95edeb07fe77454ebb346703a3fe9d6e |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-95edeb07fe77454ebb346703a3fe9d6e2025-08-20T02:08:15ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2485535EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrityLola Boutin0Mingzhi Liu1Julie Déchanet Merville2Oscar Bedoya-Reina3Margareta T Wilhelm4Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, SwedenCNRS, ImmunoConcept, UMR 5164, Bordeaux University, Bordeaux, FranceSchool of Medical Sciences, Örebro University, Örebro, SwedenDepartment of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, SwedenMedulloblastoma (MB) is a pediatric brain tumor that develops in the cerebellum, representing one of the most common malignant brain cancers in children. Standard treatments include surgery, chemotherapy, and radiation, but despite a 5-y survival rate of approximately 70%, these therapies often lead to significant neurological damage in the developing brain. This underscores the urgent need for less toxic, more effective therapeutic alternatives. Recent advancements in cancer immunotherapy, including immune checkpoint inhibitors and CAR-T cell therapy, have revolutionized cancer treatment. One promising avenue is the use of Gamma Delta (γδ)T cells, a unique T cell population with potential advantages, such as non-alloreactivity, potent tumor cell lysis, and broad antigen recognition. However, their capacity to recognize and target MB cells remains underexplored. To investigate the therapeutic potential of γδT cells against MB, we analyzed the proportion and status of MB-infiltrated γδT cells within patient datasets. We next investigated the expression of γδT cell ligands on MB cells and identified the EphA2 receptor and the phosphoantigen/Butyrophilin complex as key ligands, activating Vγ9 Vδ1 and Vγ9 Vδ2 T cells, respectively, leading to significant MB cell lysis in both monolayer and spheroid models. Importantly, preliminary safety data showed that γδT cells did not target differentiated neurons or neuroepithelial stem cells derived from induced pluripotent stem cells, underscoring the selectivity and safety of this approach. In conclusion, γδT cells trigger an efficient and specific killing of MB and would offer a promising novel therapeutic strategy.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2485535Gamma delta T cellsimmunotherapymedulloblastoma |
| spellingShingle | Lola Boutin Mingzhi Liu Julie Déchanet Merville Oscar Bedoya-Reina Margareta T Wilhelm EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity OncoImmunology Gamma delta T cells immunotherapy medulloblastoma |
| title | EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity |
| title_full | EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity |
| title_fullStr | EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity |
| title_full_unstemmed | EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity |
| title_short | EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity |
| title_sort | epha2 and phosphoantigen mediated selective killing of medulloblastoma by γδt cells preserves neuronal and stem cell integrity |
| topic | Gamma delta T cells immunotherapy medulloblastoma |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2485535 |
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