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

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  • Rebecca J. Brownlie

    (University of Edinburgh, Ashworth Laboratories
    University of Leeds, Wellcome Trust Brenner Building, St James’s University Hospital)

  • 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
    University of Leeds, Wellcome Trust Brenner Building, St James’s University Hospital)

  • Rose Zamoyska

    (University of Edinburgh, Ashworth Laboratories)

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.

Suggested Citation

  • Rebecca J. Brownlie & Celine Garcia & Mate Ravasz & Dietmar Zehn & Robert J. Salmond & Rose Zamoyska, 2017. "Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01427-1
    DOI: 10.1038/s41467-017-01427-1
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