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, Rose Zamoyska

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish
Article number1343
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2017

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