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Neuropilin 1deficiency onCD4+Foxp3+ regulatoryT cells impairs mousemelanoma growth Wiebke HansenMarina HutzlerSimone Abel2012 год

Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth
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Аннотация: 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.
Год издания: 2012
Авторы: Wiebke Hansen, Marina Hutzler, Simone Abel, Christina Alter, Christian Stockmann, Stefanie Kliche, Juliane Albert, Tim Sparwasser, Shimon Sakaguchi, Astrid M. Westendorf, Dirk Schadendorf, Jan Buer, Iris Helfrich
Издательство: Rockefeller University Press
Источник: The Journal of Experimental Medicine
Ключевые слова: Angiogenesis and VEGF in Cancer, Axon Guidance and Neuronal Signaling, Lymphatic System and Diseases
Другие ссылки: The Journal of Experimental Medicine (PDF)
The Journal of Experimental Medicine (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
HZI Open Repository (Helmholtz-Zentrum für Infektionsforschung GmbH) (PDF)
HZI Open Repository (Helmholtz-Zentrum für Infektionsforschung GmbH) (HTML)
PubMed Central (HTML)
PubMed (HTML)