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Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy

Anti-angiogenic cancer therapies possess immune-stimulatory properties by counteracting pro-angiogenic molecular mechanisms. We report that tumor endothelial cells ubiquitously overexpress and secrete the intermediate filament protein vimentin through type III unconventional secretion mechanisms. Ex...

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Autores principales: van Beijnum, Judy R., Huijbers, Elisabeth J. M., van Loon, Karlijn, Blanas, Athanasios, Akbari, Parvin, Roos, Arno, Wong, Tse J., Denisov, Stepan S., Hackeng, Tilman M., Jimenez, Connie R., Nowak-Sliwinska, Patrycja, Griffioen, Arjan W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126915/
https://www.ncbi.nlm.nih.gov/pubmed/35606362
http://dx.doi.org/10.1038/s41467-022-30063-7
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author van Beijnum, Judy R.
Huijbers, Elisabeth J. M.
van Loon, Karlijn
Blanas, Athanasios
Akbari, Parvin
Roos, Arno
Wong, Tse J.
Denisov, Stepan S.
Hackeng, Tilman M.
Jimenez, Connie R.
Nowak-Sliwinska, Patrycja
Griffioen, Arjan W.
author_facet van Beijnum, Judy R.
Huijbers, Elisabeth J. M.
van Loon, Karlijn
Blanas, Athanasios
Akbari, Parvin
Roos, Arno
Wong, Tse J.
Denisov, Stepan S.
Hackeng, Tilman M.
Jimenez, Connie R.
Nowak-Sliwinska, Patrycja
Griffioen, Arjan W.
author_sort van Beijnum, Judy R.
collection PubMed
description Anti-angiogenic cancer therapies possess immune-stimulatory properties by counteracting pro-angiogenic molecular mechanisms. We report that tumor endothelial cells ubiquitously overexpress and secrete the intermediate filament protein vimentin through type III unconventional secretion mechanisms. Extracellular vimentin is pro-angiogenic and functionally mimics VEGF action, while concomitantly acting as inhibitor of leukocyte-endothelial interactions. Antibody targeting of extracellular vimentin shows inhibition of angiogenesis in vitro and in vivo. Effective and safe inhibition of angiogenesis and tumor growth in several preclinical and clinical studies is demonstrated using a vaccination strategy against extracellular vimentin. Targeting vimentin induces a pro-inflammatory condition in the tumor, exemplified by induction of the endothelial adhesion molecule ICAM1, suppression of PD-L1, and altered immune cell profiles. Our findings show that extracellular vimentin contributes to immune suppression and functions as a vascular immune checkpoint molecule. Targeting of extracellular vimentin presents therefore an anti-angiogenic immunotherapy strategy against cancer.
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spelling pubmed-91269152022-05-25 Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy van Beijnum, Judy R. Huijbers, Elisabeth J. M. van Loon, Karlijn Blanas, Athanasios Akbari, Parvin Roos, Arno Wong, Tse J. Denisov, Stepan S. Hackeng, Tilman M. Jimenez, Connie R. Nowak-Sliwinska, Patrycja Griffioen, Arjan W. Nat Commun Article Anti-angiogenic cancer therapies possess immune-stimulatory properties by counteracting pro-angiogenic molecular mechanisms. We report that tumor endothelial cells ubiquitously overexpress and secrete the intermediate filament protein vimentin through type III unconventional secretion mechanisms. Extracellular vimentin is pro-angiogenic and functionally mimics VEGF action, while concomitantly acting as inhibitor of leukocyte-endothelial interactions. Antibody targeting of extracellular vimentin shows inhibition of angiogenesis in vitro and in vivo. Effective and safe inhibition of angiogenesis and tumor growth in several preclinical and clinical studies is demonstrated using a vaccination strategy against extracellular vimentin. Targeting vimentin induces a pro-inflammatory condition in the tumor, exemplified by induction of the endothelial adhesion molecule ICAM1, suppression of PD-L1, and altered immune cell profiles. Our findings show that extracellular vimentin contributes to immune suppression and functions as a vascular immune checkpoint molecule. Targeting of extracellular vimentin presents therefore an anti-angiogenic immunotherapy strategy against cancer. Nature Publishing Group UK 2022-05-23 /pmc/articles/PMC9126915/ /pubmed/35606362 http://dx.doi.org/10.1038/s41467-022-30063-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
van Beijnum, Judy R.
Huijbers, Elisabeth J. M.
van Loon, Karlijn
Blanas, Athanasios
Akbari, Parvin
Roos, Arno
Wong, Tse J.
Denisov, Stepan S.
Hackeng, Tilman M.
Jimenez, Connie R.
Nowak-Sliwinska, Patrycja
Griffioen, Arjan W.
Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy
title Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy
title_full Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy
title_fullStr Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy
title_full_unstemmed Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy
title_short Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy
title_sort extracellular vimentin mimics vegf and is a target for anti-angiogenic immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126915/
https://www.ncbi.nlm.nih.gov/pubmed/35606362
http://dx.doi.org/10.1038/s41467-022-30063-7
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