Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22
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...
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Published in | Nature communications Vol. 8; no. 1; pp. 1343 - 10 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
07.11.2017
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
TGFβ secretion in the tumor microenvironment inhibits T cell-mediated anti-tumor immune responses. Here the authors show that a mutation predisposing to autoimmune diseases confers T cells resistance to TGFβ inhibitory action and could be exploited to engineer immunotherapies for TGFβ secreting tumors. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-017-01427-1 |