Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Semaphorin 3A induces cytoskeletal paralysis in tumor-specific CD8+ T cells

View ORCID ProfileMike B Barnkob, View ORCID ProfileYale S Michaels, Violaine André, View ORCID ProfilePhilip S Macklin, View ORCID ProfileUzi Gileadi, View ORCID ProfileSalvatore Valvo, View ORCID ProfileMargarida Rei, View ORCID ProfileCorinna Kulicke, View ORCID ProfileJi-Li Chen, View ORCID ProfileVitul Jain, Victoria Woodcock, View ORCID ProfileHuw Colin-York, View ORCID ProfileAndreas V Hadjinicolaou, Youxin Kong, View ORCID ProfileViveka Mayya, View ORCID ProfileJoshua A Bull, View ORCID ProfilePramila Rijal, Christopher W Pugh, View ORCID ProfileAlain R Townsend, View ORCID ProfileLars R Olsen, View ORCID ProfileMarco Fritzsche, View ORCID ProfileTudor A Fulga, View ORCID ProfileMichael L Dustin, View ORCID ProfileE Yvonne Jones, View ORCID ProfileVincenzo Cerundolo
doi: https://doi.org/10.1101/849083
Mike B Barnkob
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mike B Barnkob
Yale S Michaels
2MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yale S Michaels
Violaine André
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip S Macklin
3Nuffield Department of Medicine, University of Oxford, Nuffield Department of Medicine Research Building, Roosevelt Drive, Oxford OX3 7FZ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Philip S Macklin
Uzi Gileadi
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Uzi Gileadi
Salvatore Valvo
4Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Dr, Oxford OX3 7FY, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Salvatore Valvo
Margarida Rei
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Margarida Rei
Corinna Kulicke
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Corinna Kulicke
Ji-Li Chen
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ji-Li Chen
Vitul Jain
5Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vitul Jain
Victoria Woodcock
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Huw Colin-York
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Huw Colin-York
Andreas V Hadjinicolaou
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andreas V Hadjinicolaou
Youxin Kong
5Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Viveka Mayya
4Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Dr, Oxford OX3 7FY, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Viveka Mayya
Joshua A Bull
6Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Joshua A Bull
Pramila Rijal
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pramila Rijal
Christopher W Pugh
3Nuffield Department of Medicine, University of Oxford, Nuffield Department of Medicine Research Building, Roosevelt Drive, Oxford OX3 7FZ, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alain R Townsend
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alain R Townsend
Lars R Olsen
7Department of Health Technology, Technical University of Denmark, Ørsteds Plads, Building 345C, 2800 Kgs. Lyngby, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lars R Olsen
Marco Fritzsche
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
4Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Dr, Oxford OX3 7FY, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marco Fritzsche
Tudor A Fulga
2MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tudor A Fulga
Michael L Dustin
4Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Dr, Oxford OX3 7FY, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael L Dustin
E Yvonne Jones
5Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for E Yvonne Jones
Vincenzo Cerundolo
1MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vincenzo Cerundolo
  • For correspondence: vincenzo.cerundolo@imm.ox.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Semaphorin-3A (Sema3A) regulates tumor angiogenesis, but its role in modulating anti-tumor immunity is unclear. We demonstrate that Sema3A secreted within the tumor microenvironment (TME) suppresses tumor-specific CD8+ T cell function via Neuropilin-1 (NRP1), a receptor that is upregulated upon activation with T cells’ cognate antigen. Sema3A inhibits T cell migration, assembly of the immunological synapse, and tumor killing. It achieves these functional effects through hyper-activating the acto-myosin system in T cells leading to cellular paralysis. Finally, using a clear cell renal cell carcinoma patient cohort, we demonstrate that human tumor-specific CD8+ T cells express NRP1 and are trapped in Sema3A rich regions of tumors. Our study establishes Sema3A as a potent inhibitor of anti-tumor immunity.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 20, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Semaphorin 3A induces cytoskeletal paralysis in tumor-specific CD8+ T cells
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Semaphorin 3A induces cytoskeletal paralysis in tumor-specific CD8+ T cells
Mike B Barnkob, Yale S Michaels, Violaine André, Philip S Macklin, Uzi Gileadi, Salvatore Valvo, Margarida Rei, Corinna Kulicke, Ji-Li Chen, Vitul Jain, Victoria Woodcock, Huw Colin-York, Andreas V Hadjinicolaou, Youxin Kong, Viveka Mayya, Joshua A Bull, Pramila Rijal, Christopher W Pugh, Alain R Townsend, Lars R Olsen, Marco Fritzsche, Tudor A Fulga, Michael L Dustin, E Yvonne Jones, Vincenzo Cerundolo
bioRxiv 849083; doi: https://doi.org/10.1101/849083
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Semaphorin 3A induces cytoskeletal paralysis in tumor-specific CD8+ T cells
Mike B Barnkob, Yale S Michaels, Violaine André, Philip S Macklin, Uzi Gileadi, Salvatore Valvo, Margarida Rei, Corinna Kulicke, Ji-Li Chen, Vitul Jain, Victoria Woodcock, Huw Colin-York, Andreas V Hadjinicolaou, Youxin Kong, Viveka Mayya, Joshua A Bull, Pramila Rijal, Christopher W Pugh, Alain R Townsend, Lars R Olsen, Marco Fritzsche, Tudor A Fulga, Michael L Dustin, E Yvonne Jones, Vincenzo Cerundolo
bioRxiv 849083; doi: https://doi.org/10.1101/849083

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4866)
  • Biochemistry (10821)
  • Bioengineering (8068)
  • Bioinformatics (27381)
  • Biophysics (14030)
  • Cancer Biology (11165)
  • Cell Biology (16106)
  • Clinical Trials (138)
  • Developmental Biology (8808)
  • Ecology (13332)
  • Epidemiology (2067)
  • Evolutionary Biology (17399)
  • Genetics (11705)
  • Genomics (15963)
  • Immunology (11061)
  • Microbiology (26168)
  • Molecular Biology (10680)
  • Neuroscience (56746)
  • Paleontology (422)
  • Pathology (1737)
  • Pharmacology and Toxicology (3012)
  • Physiology (4569)
  • Plant Biology (9669)
  • Scientific Communication and Education (1617)
  • Synthetic Biology (2699)
  • Systems Biology (6997)
  • Zoology (1515)