Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance

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 IFNγ or IL12p35 deficiency. Accordingly, EG7-induced tumors grew faster in IFNAR1 ^-/- and Tyk2 ^-/- but not in IFNγ ^-/- 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 Tcells were incapable of controlling EG7-induced tumor growth.