Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth.

2.50
Hdl Handle:
http://hdl.handle.net/10033/269936
Title:
Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth.
Authors:
Hansen, Wiebke; Hutzler, Marina; Abel, Simone; Alter, Christina; Stockmann, Christian; Kliche, Stefanie; Albert, Juliane; Sparwasser, Tim; Sakaguchi, Shimon; Westendorf, Astrid M; Schadendorf, Dirk; Buer, Jan; Helfrich, Iris
Abstract:
Infiltration of Foxp3(+) regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3(+) T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell-specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3(+) T reg cells were significantly reduced accompanied by enhanced activation of CD8(+) T cells within tumors of T cell-specific Nrp-1-deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1(+) T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3(+) T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression.
Affiliation:
Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. wiebke.hansen@uk-essen.de
Citation:
Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth. 2012, 209 (11):2001-16 J. Exp. Med.
Journal:
The Journal of experimental medicine
Issue Date:
22-Oct-2012
URI:
http://hdl.handle.net/10033/269936
DOI:
10.1084/jem.20111497
PubMed ID:
23045606
Type:
Article
Language:
en
ISSN:
1540-9538
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorHansen, Wiebkeen_GB
dc.contributor.authorHutzler, Marinaen_GB
dc.contributor.authorAbel, Simoneen_GB
dc.contributor.authorAlter, Christinaen_GB
dc.contributor.authorStockmann, Christianen_GB
dc.contributor.authorKliche, Stefanieen_GB
dc.contributor.authorAlbert, Julianeen_GB
dc.contributor.authorSparwasser, Timen_GB
dc.contributor.authorSakaguchi, Shimonen_GB
dc.contributor.authorWestendorf, Astrid Men_GB
dc.contributor.authorSchadendorf, Dirken_GB
dc.contributor.authorBuer, Janen_GB
dc.contributor.authorHelfrich, Irisen_GB
dc.date.accessioned2013-02-21T10:26:55Z-
dc.date.available2013-02-21T10:26:55Z-
dc.date.issued2012-10-22-
dc.identifier.citationNeuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth. 2012, 209 (11):2001-16 J. Exp. Med.en_GB
dc.identifier.issn1540-9538-
dc.identifier.pmid23045606-
dc.identifier.doi10.1084/jem.20111497-
dc.identifier.urihttp://hdl.handle.net/10033/269936-
dc.description.abstractInfiltration of Foxp3(+) regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3(+) T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell-specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3(+) T reg cells were significantly reduced accompanied by enhanced activation of CD8(+) T cells within tumors of T cell-specific Nrp-1-deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1(+) T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3(+) T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to The Journal of experimental medicineen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshCD4-Positive T-Lymphocytesen_GB
dc.subject.meshCD8-Positive T-Lymphocytesen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCell Movementen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshForkhead Transcription Factorsen_GB
dc.subject.meshGene Expression Regulation, Neoplasticen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshLymphocyte Activationen_GB
dc.subject.meshMelanoma, Experimentalen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred C57BLen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshMice, Transgenicen_GB
dc.subject.meshNeuropilin-1en_GB
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_GB
dc.subject.meshSkin Neoplasmsen_GB
dc.subject.meshT-Lymphocytes, Regulatoryen_GB
dc.subject.meshTumor Burdenen_GB
dc.subject.meshTumor Escapeen_GB
dc.subject.meshVascular Endothelial Growth Factor Aen_GB
dc.titleNeuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth.en
dc.typeArticleen
dc.contributor.departmentInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. wiebke.hansen@uk-essen.deen_GB
dc.identifier.journalThe Journal of experimental medicineen_GB

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