| First Author | Brownlie RJ | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1343 |
| PubMed ID | 29116089 | Mgi Jnum | J:257206 |
| Mgi Id | MGI:6106113 | Doi | 10.1038/s41467-017-01427-1 |
| Citation | Brownlie RJ, et al. (2017) Resistance to TGFbeta suppression and improved anti-tumor responses in CD8(+) T cells lacking PTPN22. Nat Commun 8(1):1343 |
| abstractText | Transforming growth factor beta (TGFbeta) 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 TGFbeta. Resistance to TGFbeta suppression, while disadvantageous in autoimmunity, helps Ptpn22 (-/-) T cells to be intrinsically superior at clearing established tumors that secrete TGFbeta. Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce IL-2, which overcomes TGFbeta-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. |
