| First Author | Simma O | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 1 | Pages | 203-11 |
| PubMed ID | 19118004 | Mgi Jnum | J:143032 |
| Mgi Id | MGI:3822678 | Doi | 10.1158/0008-5472.CAN-08-1705 |
| Citation | Simma O, et al. (2009) Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance. Cancer Res 69(1):203-11 |
| abstractText | We showed previously that Tyk2(-/-) natural killer cells lack the ability to lyse leukemic cells. As a consequence, the animals are leukemia prone. Here, we show that the impaired tumor surveillance extends to T cells. Challenging Tyk2(-/-) mice with EL4 thymoma significantly decreased disease latency. The crucial role of Tyk2 for CTL function was further characterized using the ovalbumin-expressing EG7 cells. Tyk2(-/-) OT-1 mice developed EG7-induced tumors significantly faster compared with wild-type (wt) controls. In vivo assays confirmed the defect in CD8(+) cytotoxicity on Tyk2 deficiency and clearly linked it to type I IFN signaling. An impaired CTL activity was only observed in IFNAR1(-/-) animals but not on IFNgamma or IL12p35 deficiency. Accordingly, EG7-induced tumors grew faster in IFNAR1(-/-) and Tyk2(-/-) but not in IFNgamma(-/-) or IL12p35(-/-) mice. Adoptive transfer experiments defined a key role of Tyk2 in CTL-mediated tumor surveillance. In contrast to wt OT-1 cells, Tyk2(-/-) OT-1 T cells were incapable of controlling EG7-induced tumor growth. |
