Neuropilin 1: function and therapeutic potential in cancer
Open accessAbstract
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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Nrp1 is not required to inhibit autoimmunity and maintain immunological homeostasis.
“Nrp1 is not required to inhibit autoimmunity and maintain immunological homeostasis [47, 48].”
From Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review (2024) · cites this paper as [48]
The Concluding remarks report that NRP1 blockade does not significantly affect immune suppression in humans, which supports a narrower version of the claim. But the same passage says blockade abrogates immunosuppressive function in mice, and the passage on experimental autoimmune encephalomyelitis reports rapid disease progression with NRP1 deficiency. The paper therefore does not support the unqualified claim that NRP1 is unnecessary for inhibiting autoimmunity and maintaining immunological homeostasis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe fragile Tregs subset is associated with a better prognosis in patients with metastatic melanoma and head and neck squamous cell cancer.
“The fragile Tregs subset is associated with a better prognosis in patients with metastatic melanoma and HNSCC.”
From Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review (2024) · cites this paper as [48]
The section headed “Tregs and Neuropilin 1 in cancer” (page unavailable) links Treg accumulation generally to worsening prognosis, but does not discuss a fragile Treg subset. Searches for fragile Tregs and for prognosis in metastatic melanoma and HNSCC found no passage addressing the claimed association; the general Treg finding does not rule out a different association for that subset. (LLM, conf=0.76)
Experimental — accuracy not yet measuredHigh levels of VEGF promote recruitment and proliferation of regulatory T cells, myeloid-derived suppressor cells and pro-tumour M2-like tumour-associated macrophages.
“Third, high levels of VEGF promote the recruitment and proliferation of immunosuppressive cells, including Treg cells, MDSCs, and pro-tumour, M2-like TAMs25,26”
From Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges (2018) · cites this paper as [26]
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References 151 · Cited by 233
- Authors
- Chaudhary, B., Khaled, Y. S., Ammori, B. J., & Elkord, E.
- Affiliations
- University of Salford (GB)
- University of Manchester (GB)
- United Arab Emirates University (AE)
- Corresponding author
- Elkord, Eyad
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2013-11-22
- Volume
- 63
- Issue
- 2
- Pages
- 81-99
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC11028473
- OpenAlex
- W2073775185
- Cited by
- 233
- References
- 151
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 19 · 2023: 24 · 2022: 20 · 2021: 23 · 2020: 26 · 2019: 14 · 2018: 14 · 2017: 21 · 2016: 15 · 2015: 16 · 2014: 9
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2012-02-007)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- neuropilin-1, regulatory T cells, plasmacytoid dendritic cells, tumor immunosuppression, semaphorins, vascular endothelial growth factor, TGF-beta, T cell activation, cell-penetrating peptides, cancer immunotherapy
- MeSH terms
- Animals, Dendritic Cells, Humans, Lymphocyte Activation, Neoplasms, Transforming Growth Factor beta, Proto-Oncogene Proteins c-met, Neuropilin-1, Semaphorins, Semaphorin-3A, Vascular Endothelial Growth Factor A, T-Lymphocytes, Regulatory
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