Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22

Rebecca J. Brownlie, Celine Garcia, Mate Ravasz, Dietmar Zehn, Robert J. Salmond () and Rose Zamoyska ()
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Rebecca J. Brownlie: University of Edinburgh, Ashworth Laboratories
Celine Garcia: University of Edinburgh, Ashworth Laboratories
Mate Ravasz: University of Edinburgh, Ashworth Laboratories
Dietmar Zehn: Technical University Munich
Robert J. Salmond: University of Edinburgh, Ashworth Laboratories
Rose Zamoyska: University of Edinburgh, Ashworth Laboratories

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01427-1

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