Double hit strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells

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dc.authorscopusid56364984200
dc.authorscopusid56364164300
dc.authorscopusid56120090200
dc.authorscopusid56376463500
dc.authorscopusid6701658370
dc.authorscopusid56009604300
dc.authorwosidAcikgoz, eda/W-2171-2017
dc.contributor.authorAcikgoz, Eda
dc.contributor.authorDuzagac, Fahriye
dc.contributor.authorGuven, Ummu
dc.contributor.authorYigitturk, Gurkan
dc.contributor.authorKose, Timur
dc.contributor.authorOktem, Gulperi
dc.date.accessioned2023-01-12T19:55:06Z
dc.date.available2023-01-12T19:55:06Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractCancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44+/CD24-/low breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.en_US
dc.description.sponsorshipEge University Faculty of Medicine Histology and Embryology Laboratoriesen_US
dc.description.sponsorshipPartial financial support was received from the <spacing diaeresis>OYP (Academician training program of Turkey) and Ege University Faculty of Medicine Histology and Embryology Laboratories.en_US
dc.identifier.doi10.1016/j.intimp.2022.108684
dc.identifier.issn1567-5769
dc.identifier.issn1878-1705
dc.identifier.pmid35272171en_US
dc.identifier.scopus2-s2.0-85125732379en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.intimp.2022.108684
dc.identifier.urihttps://hdl.handle.net/11454/76611
dc.identifier.volume107en_US
dc.identifier.wosWOS:000884432600001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofInternational Immunopharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCancer stem cellen_US
dc.subjectDendritic cellen_US
dc.subjectSialic aciden_US
dc.subjectTumor lysateen_US
dc.subjectMetastasisen_US
dc.subjectBreast canceren_US
dc.subjectImmune-Responseen_US
dc.subjectMaturationen_US
dc.subjectPodosomesen_US
dc.subjectImmunotherapyen_US
dc.subjectApoptosisen_US
dc.subjectGelsolinen_US
dc.subjectNecrosisen_US
dc.subjectMiceen_US
dc.titleDouble hit strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cellsen_US
dc.typeArticleen_US

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