Academic Journal
Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
| العنوان: | Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands |
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| المؤلفون: | Raute, Katrin, Strietz, Juliane, Parigiani, Maria Alejandra, Andrieux, Geoffroy, Thomas, Oliver S., Kistner, Klaus M., Zintchenko, Marina, Aichele, Peter, Hofmann, Maike, Zhou, Houjiang, Weber, Wilfried, Boerries, Melanie, Swamy, Mahima, Maurer, Jochen, Minguet, Susana |
| بيانات النشر: | AACR |
| سنة النشر: | 2023 |
| المجموعة: | LeibnizOpen (The Leibniz Association) |
| مصطلحات موضوعية: | Animals, Humans, Mice, Monitoring, Immunologic, Neoplasm Recurrence, Local, Neoplastic Stem Cells, Receptors, Antigen, T-Cell, gamma-delta, Triple Negative Breast Neoplasms, alpha interferon, cell adhesion molecule, compactin, matrix metalloproteinase 14, nivolumab, proteome, zoledronic acid, lymphocyte antigen receptor, animal cell, animal experiment, animal model, antigen recognition, antigenic escape, Article, breast cancer, cancer immunotherapy |
| Time: | 610 |
| الوصف: | There are no targeted therapies for patients with triple-negative breast cancer (TNBC). TNBC is enriched in breast cancer stem cells (BCSC), which play a key role in metastasis, chemoresistance, relapse, and mortality. γδ T cells hold great potential in immunotherapy against cancer and might provide an approach to therapeutically target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor-sensing mechanisms, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. Herein, we show that patient-derived triple-negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γ δ T-cell immunotherapy. We unraveled concerted differentiation and immune escape mechanisms: xenografted BCSCs lost stemness, expression of γ δ T-cell ligands, adhesion molecules, and pAgs, thereby evading immune recognition by γ δ T cells. Indeed, neither promigratory engineered γ δ T cells, nor anti–PD-1 checkpoint blockade, significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γ δ T cells and could be pharmacologically reverted by zoledronate or IFNα treatment. These results pave the way for novel combinatorial immunotherapies for TNBC. ; publishedVersion |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.34657/13696 |
| الاتاحة: | https://oa.tib.eu/renate/handle/123456789/14674 https://doi.org/10.34657/13696 |
| Rights: | CC BY 4.0 Unported ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.3A24B8FA |
| قاعدة البيانات: | BASE |
| DOI: | 10.34657/13696 |
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