regulatory T cells impairs mouse melanoma growth

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 pheno type 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 infiltra tion into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression.