Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Westendorf, Astrid M
MetadataShow full item record
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.
CitationNeuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth. 2012, 209 (11):2001-16 J. Exp. Med.
AffiliationInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. email@example.com
The following license files are associated with this item:
- Platelet-derived growth factor-producing CD4+ Foxp3+ regulatory T lymphocytes promote lung fibrosis.
- Authors: Lo Re S, Lecocq M, Uwambayinema F, Yakoub Y, Delos M, Demoulin JB, Lucas S, Sparwasser T, Renauld JC, Lison D, Huaux F
- Issue date: 2011 Dec 1
- Foxp3 expression in melanoma cells as a possible mechanism of resistance to immune destruction.
- Authors: Niu J, Jiang C, Li C, Liu L, Li K, Jian Z, Gao T
- Issue date: 2011 Aug
- Characterisation of Foxp3 splice variants in human CD4+ and CD8+ T cells--identification of Foxp3Δ7 in human regulatory T cells.
- Authors: Kaur G, Goodall JC, Jarvis LB, Hill Gaston JS
- Issue date: 2010 Nov-Dec
- Cellular and cytokine-dependent immunosuppressive mechanisms of grm1-transgenic murine melanoma.
- Authors: Alb M, Sie C, Adam C, Chen S, Becker JC, Schrama D
- Issue date: 2012 Dec
- Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis.
- Authors: Jacobo P, Guazzone VA, Jarazo-Dietrich S, Theas MS, Lustig L
- Issue date: 2009 Jul