Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7976
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dc.contributor.authorTrojandt, Stefanie-
dc.contributor.authorReske-Kunz, Angelika B.-
dc.contributor.authorBros, Matthias-
dc.date.accessioned2022-10-13T09:18:35Z-
dc.date.available2022-10-13T09:18:35Z-
dc.date.issued2014-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7991-
dc.description.abstractBACKGROUND: The chaperon heat shock protein 90 (HSP90) constitutes an important target for anti-tumor therapy due to its essential role in the stabilization of oncogenes. However, HSP90 is ubiquitously active to orchestrate protein turnover, chemotherapeutics that target HSP90 may affect immune cells as a significant side effect. Therefore, we asked for potential effects of pharmacological HSP90 inhibition at a therapeutically relevant concentration on human dendritic cells (DCs) as main inducers of both cellular and humoral immune responses, and on human CD4(+) T cells as directly activated by DCs and essential to confer B cell help. METHODS: Unstimulated human monocyte-derived DCs (MO-DCs) were treated with the prototypical HSP90 inhibitor geldanamycin (GA). Based on dose titration studies performed to assess cytotoxic effects, GA was applied at a rather low concentration, comparable to serum levels of clinically used HSP90 inhibitors. The immuno-phenotype (surface markers, cytokines), migratory capacity, allo T cell stimulatory and polarizing properties (proliferation, cytokine pattern) of GA-treated MO-DCs were assessed. Moreover, effects of GA on resting and differentially stimulated CD4(+) T cells in terms of cytotoxicity and proliferation were analysed. RESULTS: GA induced partial activation of unstimulated MO-DCs. In contrast, when coapplied in the course of MO-DC stimulation, GA prevented the acquisition of a fully mature DC phenotype. Consequently, this MO-DC population exerted lower allo CD4(+) T cell stimulation and cytokine production. Furthermore, GA exerted no cytotoxic effect on resting T cells, but abrogated proliferation of T cells stimulated by MO-DCs at either state of activation or by stimulatory antibodies. CONCLUSION: HSP90 inhibitors at clinically relevant concentrations may modulate adaptive immune responses both on the level of DC activation and T cell proliferation. Surprisingly, unstimulated DCs may be partially activated by that agent. However, due to the potent detrimental effects of HSP90 inhibitors on stimulated CD4(+) T cells, as an outcome a patients T cell responses might be impaired. Therefore, HSP90 inhibitors most probably are not suitable for treatment in combination with immunotherapeutic approaches aimed to induce DC/T cell activation.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/2.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleGeldanamycin-mediated inhibition of heat shock protein 90 partially activates dendritic cells, but interferes with their full maturation, accompanied by impaired upregulation of RelBen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7976-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleJournal of experimental & clinical cancer researchde
jgu.journal.volume33de
jgu.pages.alternativeArt. 16de
jgu.publisher.year2014-
jgu.publisher.nameBioMed centralde
jgu.publisher.placeLondonde
jgu.publisher.urihttp://dx.doi.org/10.1186/1756-9966-33-16de
jgu.publisher.issn1756-9966de
jgu.publisher.issn0392-9078de
jgu.organisation.placeMainz-
jgu.identifier.pmid24524692-
jgu.subject.ddccode610de
opus.date.modified2018-08-09T08:27:46Z-
opus.subject.dfgcode00-000-
opus.organisation.stringFB 04: Medizin: Hautklinikde_DE
opus.identifier.opusid27368-
opus.importsourcepubmed-
opus.institute.number0431-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN
opus.affiliatedReske-Kunz, Angelika B.-
opus.affiliatedBros, Matthias-
jgu.publisher.doi10.1186/1756-9966-33-16de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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