Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands

dc.bibliographicCitation.firstPage810
dc.bibliographicCitation.issue6
dc.bibliographicCitation.journalTitleCancer Immunology Researcheng
dc.bibliographicCitation.lastPage829
dc.bibliographicCitation.volume11
dc.contributor.authorRaute, Katrin
dc.contributor.authorStrietz, Juliane
dc.contributor.authorParigiani, Maria Alejandra
dc.contributor.authorAndrieux, Geoffroy
dc.contributor.authorThomas, Oliver S.
dc.contributor.authorKistner, Klaus M.
dc.contributor.authorZintchenko, Marina
dc.contributor.authorAichele, Peter
dc.contributor.authorHofmann, Maike
dc.contributor.authorZhou, Houjiang
dc.contributor.authorWeber, Wilfried
dc.contributor.authorBoerries, Melanie
dc.contributor.authorSwamy, Mahima
dc.contributor.authorMaurer, Jochen
dc.contributor.authorMinguet, Susana
dc.date.accessioned2024-06-11T06:52:55Z
dc.date.available2024-06-11T06:52:55Z
dc.date.issued2023
dc.description.abstractThere 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.versionpublishedVersioneng
dc.identifier.urihttps://oa.tib.eu/renate/handle/123456789/14674
dc.identifier.urihttps://doi.org/10.34657/13696
dc.language.isoeng
dc.publisherPhiladelphia, Pa. : AACR
dc.relation.doihttps://doi.org/10.1158/2326-6066.cir-22-0296
dc.relation.essn2326-6074
dc.relation.issn2326-6066
dc.rights.licenseCC BY 4.0 Unported
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subject.ddc610
dc.subject.otherAnimalseng
dc.subject.otherHumanseng
dc.subject.otherMiceeng
dc.subject.otherMonitoring, Immunologiceng
dc.subject.otherNeoplasm Recurrence, Localeng
dc.subject.otherNeoplastic Stem Cellseng
dc.subject.otherReceptors, Antigen, T-Cell, gamma-deltaeng
dc.subject.otherTriple Negative Breast Neoplasmseng
dc.subject.otheralpha interferoneng
dc.subject.othercell adhesion moleculeeng
dc.subject.othercompactineng
dc.subject.othermatrix metalloproteinase 14eng
dc.subject.othernivolumabeng
dc.subject.otherproteomeeng
dc.subject.otherzoledronic acideng
dc.subject.otherlymphocyte antigen receptoreng
dc.subject.otheranimal celleng
dc.subject.otheranimal experimenteng
dc.subject.otheranimal modeleng
dc.subject.otherantigen recognitioneng
dc.subject.otherantigenic escapeeng
dc.subject.otherArticleeng
dc.subject.otherbreast cancereng
dc.subject.othercancer immunotherapyeng
dc.subject.othercancer stem celleng
dc.subject.othercell differentiationeng
dc.subject.othercell expansioneng
dc.subject.otherchromium release assayeng
dc.subject.othercontrolled studyeng
dc.subject.othercytotoxicityeng
dc.subject.otherenzyme activityeng
dc.subject.otherex vivo studyeng
dc.subject.otherfibroblasteng
dc.subject.otherflow cytometryeng
dc.subject.othergamma delta T lymphocyteeng
dc.subject.otherhumaneng
dc.subject.otherhuman celleng
dc.subject.otherimmune responseeng
dc.subject.otherimmunosurveillanceeng
dc.subject.otherin vivo studyeng
dc.subject.othermass spectrometryeng
dc.subject.othermouseeng
dc.subject.othernonhumaneng
dc.subject.otheroverall survivaleng
dc.subject.otherperipheral blood mononuclear celleng
dc.subject.otherreversed phase liquid chromatographyeng
dc.subject.otherRNA sequencingeng
dc.subject.otherSanger sequencingeng
dc.subject.otherscanning electron microscopyeng
dc.subject.othertranswell assayeng
dc.subject.othertriple negative breast cancereng
dc.subject.otherupregulationeng
dc.subject.otherxenotransplantationeng
dc.subject.otheranimaleng
dc.subject.othercancer stem celleng
dc.subject.otherimmunological monitoringeng
dc.subject.othermetabolismeng
dc.subject.otherpathologyeng
dc.subject.othertriple negative breast cancereng
dc.subject.othertumor recurrenceeng
dc.titleBreast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligandseng
dc.typeArticleeng
dc.typeTexteng
tib.accessRightsopenAccess
wgl.contributorINM
wgl.subjectMedizin, Gesundheitger
wgl.typeZeitschriftenartikelger
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