Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
dc.bibliographicCitation.firstPage | 810 | |
dc.bibliographicCitation.issue | 6 | |
dc.bibliographicCitation.journalTitle | Cancer Immunology Research | eng |
dc.bibliographicCitation.lastPage | 829 | |
dc.bibliographicCitation.volume | 11 | |
dc.contributor.author | Raute, Katrin | |
dc.contributor.author | Strietz, Juliane | |
dc.contributor.author | Parigiani, Maria Alejandra | |
dc.contributor.author | Andrieux, Geoffroy | |
dc.contributor.author | Thomas, Oliver S. | |
dc.contributor.author | Kistner, Klaus M. | |
dc.contributor.author | Zintchenko, Marina | |
dc.contributor.author | Aichele, Peter | |
dc.contributor.author | Hofmann, Maike | |
dc.contributor.author | Zhou, Houjiang | |
dc.contributor.author | Weber, Wilfried | |
dc.contributor.author | Boerries, Melanie | |
dc.contributor.author | Swamy, Mahima | |
dc.contributor.author | Maurer, Jochen | |
dc.contributor.author | Minguet, Susana | |
dc.date.accessioned | 2024-06-11T06:52:55Z | |
dc.date.available | 2024-06-11T06:52:55Z | |
dc.date.issued | 2023 | |
dc.description.abstract | 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. | eng |
dc.description.version | publishedVersion | eng |
dc.identifier.uri | https://oa.tib.eu/renate/handle/123456789/14674 | |
dc.identifier.uri | https://doi.org/10.34657/13696 | |
dc.language.iso | eng | |
dc.publisher | Philadelphia, Pa. : AACR | |
dc.relation.doi | https://doi.org/10.1158/2326-6066.cir-22-0296 | |
dc.relation.essn | 2326-6074 | |
dc.relation.issn | 2326-6066 | |
dc.rights.license | CC BY 4.0 Unported | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject.ddc | 610 | |
dc.subject.other | Animals | eng |
dc.subject.other | Humans | eng |
dc.subject.other | Mice | eng |
dc.subject.other | Monitoring, Immunologic | eng |
dc.subject.other | Neoplasm Recurrence, Local | eng |
dc.subject.other | Neoplastic Stem Cells | eng |
dc.subject.other | Receptors, Antigen, T-Cell, gamma-delta | eng |
dc.subject.other | Triple Negative Breast Neoplasms | eng |
dc.subject.other | alpha interferon | eng |
dc.subject.other | cell adhesion molecule | eng |
dc.subject.other | compactin | eng |
dc.subject.other | matrix metalloproteinase 14 | eng |
dc.subject.other | nivolumab | eng |
dc.subject.other | proteome | eng |
dc.subject.other | zoledronic acid | eng |
dc.subject.other | lymphocyte antigen receptor | eng |
dc.subject.other | animal cell | eng |
dc.subject.other | animal experiment | eng |
dc.subject.other | animal model | eng |
dc.subject.other | antigen recognition | eng |
dc.subject.other | antigenic escape | eng |
dc.subject.other | Article | eng |
dc.subject.other | breast cancer | eng |
dc.subject.other | cancer immunotherapy | eng |
dc.subject.other | cancer stem cell | eng |
dc.subject.other | cell differentiation | eng |
dc.subject.other | cell expansion | eng |
dc.subject.other | chromium release assay | eng |
dc.subject.other | controlled study | eng |
dc.subject.other | cytotoxicity | eng |
dc.subject.other | enzyme activity | eng |
dc.subject.other | ex vivo study | eng |
dc.subject.other | fibroblast | eng |
dc.subject.other | flow cytometry | eng |
dc.subject.other | gamma delta T lymphocyte | eng |
dc.subject.other | human | eng |
dc.subject.other | human cell | eng |
dc.subject.other | immune response | eng |
dc.subject.other | immunosurveillance | eng |
dc.subject.other | in vivo study | eng |
dc.subject.other | mass spectrometry | eng |
dc.subject.other | mouse | eng |
dc.subject.other | nonhuman | eng |
dc.subject.other | overall survival | eng |
dc.subject.other | peripheral blood mononuclear cell | eng |
dc.subject.other | reversed phase liquid chromatography | eng |
dc.subject.other | RNA sequencing | eng |
dc.subject.other | Sanger sequencing | eng |
dc.subject.other | scanning electron microscopy | eng |
dc.subject.other | transwell assay | eng |
dc.subject.other | triple negative breast cancer | eng |
dc.subject.other | upregulation | eng |
dc.subject.other | xenotransplantation | eng |
dc.subject.other | animal | eng |
dc.subject.other | cancer stem cell | eng |
dc.subject.other | immunological monitoring | eng |
dc.subject.other | metabolism | eng |
dc.subject.other | pathology | eng |
dc.subject.other | triple negative breast cancer | eng |
dc.subject.other | tumor recurrence | eng |
dc.title | Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands | eng |
dc.type | Article | eng |
dc.type | Text | eng |
tib.accessRights | openAccess | |
wgl.contributor | INM | |
wgl.subject | Medizin, Gesundheit | ger |
wgl.type | Zeitschriftenartikel | ger |
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