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Resistance to TGF? suppression and improved anti-tumor responses in CD8(+) T
cells lacking PTPN22
#MMPMID29116089
Brownlie RJ
; Garcia C
; Ravasz M
; Zehn D
; Salmond RJ
; Zamoyska R
Nat Commun
2017[Nov]; 8
(1
): 1343
PMID29116089
show ga
Transforming growth factor ? (TGF?) 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 TGF?. Resistance to TGF? suppression,
while disadvantageous in autoimmunity, helps Ptpn22 (-/-) T cells to be
intrinsically superior at clearing established tumors that secrete TGF?.
Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce
IL-2, which overcomes TGF?-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.
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