Brownlie, RJ orcid.org/0000-0003-4897-1044, Garcia, C, Ravasz, M et al. (3 more authors) (2017) Resistance to TGFβ suppression and improved anti-tumor responses in CD8⁺ T cells lacking PTPN22. Nature Communications, 8. 1343. ISSN 2041-1723
Abstract
Transforming growth factor β (TGFβ) is important in maintaining self-tolerance and inhibits T cell reactivity. We show that CD8⁺ T cells that lack the tyrosine phosphatase Ptpn22, a major predisposing gene for autoimmune disease, are resistant to the suppressive effects of TGFβ. Resistance to TGFβ suppression, while disadvantageous in autoimmunity, helps Ptpn22‾/‾ T cells to be intrinsically superior at clearing established tumors that secrete TGFβ. Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce IL-2, which overcomes TGFβ-mediated suppression. These data suggest that a viable strategy to improve anti-tumor adoptive cell therapy may be to engineer tumor-restricted T cells with mutations identified as risk factors for autoimmunity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017, The Author(s). 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 https://creativecommons.org/licenses/by/4.0/. |
Keywords: | cancer immunotherapy; cancer microenviroment; immunization |
Dates: |
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Institution: | The University of Leeds |
Funding Information: | Funder Grant number Cancer Research UK C55663/A23269 |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Nov 2017 16:24 |
Last Modified: | 28 Jan 2020 15:09 |
Status: | Published |
Publisher: | Springer Nature |
Identification Number: | 10.1038/s41467-017-01427-1 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:123669 |