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Neuropilin 1: function and therapeutic potential in cancer

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Abstract

Neuropilin 1 (NRP1) is a transmembrane glycoprotein that acts as a co-receptor for a number of extracellular ligands including class III/IV semaphorins, certain isoforms of vascular endothelial growth factor and transforming growth factor beta. An exact understanding of the role of NRP1 in the immune system has been obscured by the differences in NRP1 expression observed between mice and humans. In mice, NRP1 is selectively expressed on thymic-derived Tregs and greatly enhances immunosuppressive function. In humans, NRP1 is expressed on plasmacytoid dendritic cells (pDCs) where it aids in priming immune responses and on a subset of T regulatory cells (Tregs) isolated from secondary lymph nodes. Preliminary studies that show NRP1 expression on T cells confers enhanced immunosuppressive activity. However, the mechanism by which this activity is mediated remains unclear. NRP1 expression has also been identified on activated T cells and Tregs isolated from inflammatory microenvironments, suggesting NRP1 might represent a novel T cell activation marker. Of clinical interest, NRP1 may enhance Treg tumour infiltration and a decrease in NRP1+ Tregs correlates with successful chemotherapy, suggesting a specific role for NRP1 in cancer pathology. As a therapeutic target, NRP1 allows simultaneous targeting of NRP1-expressing tumour vasculature, NRP1+ Tregs and pDCs. With the development of anti-NRP1 monoclonal antibodies and cell-penetrating peptides, NRP1 represents a promising new target for cancer therapies. This paper reviews current knowledge on the role and function of NRP1 in Tregs and pDCs, both in physiological and cancer settings, as well as its potential as a therapeutic target in cancer.

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Authors and Affiliations

  1. Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, The Crescent, Peel Building G25, Manchester, M5 4WT, UK

    Belal Chaudhary, Yazan S. Khaled, Basil J. Ammori & Eyad Elkord

  2. Institutes of Cancer, Inflammation & Repair, University of Manchester, Manchester, UK

    Yazan S. Khaled, Basil J. Ammori & Eyad Elkord

  3. College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates

    Eyad Elkord

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  1. Belal Chaudhary
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Chaudhary, B., Khaled, Y.S., Ammori, B.J. et al. Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother 63, 81–99 (2014). https://doi.org/10.1007/s00262-013-1500-0

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