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  2. Johannes Gutenberg-Universität Mainz
  3. DFG-491381577-G
Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-10047
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dc.contributor.authorBartneck, Joschka-
dc.contributor.authorHartmann, Ann-Kathrin-
dc.contributor.authorStein, Lara-
dc.contributor.authorArnold-Schild, Danielle-
dc.contributor.authorKlein, Matthias-
dc.contributor.authorStassen, Michael-
dc.contributor.authorMarini, Federico-
dc.contributor.authorPielenhofer, Jonas-
dc.contributor.authorMeiser, Sophie Luise-
dc.contributor.authorLangguth, Peter-
dc.contributor.authorMack, Matthias-
dc.contributor.authorMuth, Sabine-
dc.contributor.authorProbst, Hans-Christian-
dc.contributor.authorSchild, Hansjörg-
dc.contributor.authorRadsak, Markus Philipp-
dc.date.accessioned2024-02-19T09:43:49Z-
dc.date.available2024-02-19T09:43:49Z-
dc.date.issued2023-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/10065-
dc.description.abstractTumor development and progression is shaped by the tumor microenvironment (TME), a heterogeneous assembly of infiltrating and resident host cells, their secreted mediators and intercellular matrix. In this context, tumors are infiltrated by various immune cells with either pro-tumoral or anti-tumoral functions. Recently, we published our non-invasive immunization platform DIVA suitable as a therapeutic vaccination method, further optimized by repeated application (DIVA2). In our present work, we revealed the therapeutic effect of DIVA2 in an MC38 tumor model and specifically focused on the mechanisms induced in the TME after immunization. DIVA2 resulted in transient tumor control followed by an immune evasion phase within three weeks after the initial tumor inoculation. High-dimensional flow cytometry analysis and single-cell mRNA-sequencing of tumor-infiltrating leukocytes revealed cytotoxic CD8+ T cells as key players in the immune control phase. In the immune evasion phase, inflammatory CCR2+ PDL-1+ monocytes with immunosuppressive properties were recruited into the tumor leading to suppression of DIVA2-induced tumor-reactive T cells. Depletion of CCR2+ cells with specific antibodies resulted in prolonged survival revealing CCR2+ monocytes as important for tumor immune escape in the TME. In summary, the present work provides a platform for generating a strong antigen-specific primary and memory T cell immune response using the optimized transcutaneous immunization method DIVA2. This enables protection against tumors by therapeutic immune control of solid tumors and highlights the immunosuppressive influence of tumor infiltrating CCR2+ monocytes that need to be inactivated in addition for successful cancer immunotherapy.en_GB
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleTumor-infiltrating CCR2+ inflammatory monocytes counteract specific immunotherapyen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-10047-
jgu.type.contenttypeScientific articlede
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.titleFrontiers in immunologyde
jgu.journal.volume14de
jgu.pages.alternative1267866de
jgu.publisher.year2023-
jgu.publisher.nameFrontiers Media S.A.de
jgu.publisher.placeSwitzerlandde
jgu.publisher.issn1664-3224de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.3389/fimmu.2023.1267866de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgLebenswissenschaftende
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