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Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice

Cancer cells are poorly immunogenic and have a wide range of mutations, which makes them unsuitable for use in vaccination treatment. Here, we show that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significan...

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Autores principales: Li, Yang, Zhang, Mingyou, Wang, Xiaodan, Liu, Wentao, Wang, Hui, Yang, Yong-Guang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989506/
https://www.ncbi.nlm.nih.gov/pubmed/31996683
http://dx.doi.org/10.1038/s41467-019-14102-4
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author Li, Yang
Zhang, Mingyou
Wang, Xiaodan
Liu, Wentao
Wang, Hui
Yang, Yong-Guang
author_facet Li, Yang
Zhang, Mingyou
Wang, Xiaodan
Liu, Wentao
Wang, Hui
Yang, Yong-Guang
author_sort Li, Yang
collection PubMed
description Cancer cells are poorly immunogenic and have a wide range of mutations, which makes them unsuitable for use in vaccination treatment. Here, we show that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significantly improves the effectiveness of the immune response to tumour cells. In both solid and hematopoietic mouse tumor models, vaccination with tumor cells or tumor antigen-expressing cells, that lack CD47 or were pre-coated with anti-CD47 antibodies, achieved an antitumor immune response. The efficacy of this approach was synergistically enhanced when used in combination with anti-PD-1 antibodies. The induction of antitumor responses depends on SIRPα(+)CD11c(+) DCs, which exhibit rapid expansion following introduction of CD47-deficient tumor cells. Our results indicate that CD47-deficient whole tumor cells can induce antitumor responses.
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spelling pubmed-69895062020-01-31 Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice Li, Yang Zhang, Mingyou Wang, Xiaodan Liu, Wentao Wang, Hui Yang, Yong-Guang Nat Commun Article Cancer cells are poorly immunogenic and have a wide range of mutations, which makes them unsuitable for use in vaccination treatment. Here, we show that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significantly improves the effectiveness of the immune response to tumour cells. In both solid and hematopoietic mouse tumor models, vaccination with tumor cells or tumor antigen-expressing cells, that lack CD47 or were pre-coated with anti-CD47 antibodies, achieved an antitumor immune response. The efficacy of this approach was synergistically enhanced when used in combination with anti-PD-1 antibodies. The induction of antitumor responses depends on SIRPα(+)CD11c(+) DCs, which exhibit rapid expansion following introduction of CD47-deficient tumor cells. Our results indicate that CD47-deficient whole tumor cells can induce antitumor responses. Nature Publishing Group UK 2020-01-29 /pmc/articles/PMC6989506/ /pubmed/31996683 http://dx.doi.org/10.1038/s41467-019-14102-4 Text en © The Author(s) 2020 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/.
spellingShingle Article
Li, Yang
Zhang, Mingyou
Wang, Xiaodan
Liu, Wentao
Wang, Hui
Yang, Yong-Guang
Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
title Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
title_full Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
title_fullStr Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
title_full_unstemmed Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
title_short Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
title_sort vaccination with cd47 deficient tumor cells elicits an antitumor immune response in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989506/
https://www.ncbi.nlm.nih.gov/pubmed/31996683
http://dx.doi.org/10.1038/s41467-019-14102-4
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