In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 1 ( 2009-01-01), p. 203-211
Abstract:
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 T cells were incapable of controlling EG7-induced tumor growth. [Cancer Res 2009;69(1):203–11]
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-08-1705
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2009
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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