This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Simma, O. Articles by Stoiber, D. Search for Related Content PubMed PubMed Citation Articles by Simma, O. Articles by Stoiber, D.

Identification of an Indispensable Role for Tyrosine Kinase 2 in CTL-Mediated Tumor Surveillance

¹ Institute of Pharmacology and ² Institute of Immunology, Medical University of Vienna; ³ Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna; ⁴ Children's Cancer Research Institute, St. Anna Kinderkrebsforschung; ⁵ Intercell AG, Campus Vienna Biocenter; ⁶ Ludwig Boltzmann Institute for Cancer Research; ⁷ Institute of Animal Breeding and Genetics, Veterinary University of Vienna; and ⁸ University Center for Biomodels Austria VUW, Vienna, Austria

Requests for reprints: Dagmar Stoiber, Institute of Pharmacology, Medical University of Vienna, Waehringerstrasse 13A, A-1090 Vienna, Austria. Phone: 43-1-4277-64130; Fax: 43-1-4277-9641; E-mail: dagmar.stoiber{at}meduniwien.ac.at.

Key Words: Tyk2 • tumor surveillance • CTL

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 IFN or IL12p35 deficiency. Accordingly, EG7-induced tumors grew faster in IFNAR1^–/– and Tyk2^–/– but not in IFN^–/– 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]