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TYK2 in Tumor Immunosurveillance

Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, A-1210 Vienna, Austria
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Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Center for Anatomy and Cell Biology, Medical University of Vienna, A-1090 Vienna, Austria.
§
These authors contributed equally to this work.
Cancers 2020, 12(1), 150; https://doi.org/10.3390/cancers12010150
Received: 29 November 2019 / Revised: 20 December 2019 / Accepted: 25 December 2019 / Published: 8 January 2020
(This article belongs to the Special Issue JAK-STAT Signalling Pathway in Cancer)
We review the history of the tyrosine kinase 2 (TYK2) as the founding member of the Janus kinase (JAK) family and outline its structure-function relation. Gene-targeted mice and hereditary defects of TYK2 in men have established the biological and pathological functions of TYK2 in innate and adaptive immune responses to infection and cancer and in (auto-)inflammation. We describe the architecture of the main cytokine receptor families associated with TYK2, which activate signal transducers and activators of transcription (STATs). We summarize the cytokine receptor activities with well characterized dependency on TYK2, the types of cells that respond to cytokines and TYK2 signaling-induced cytokine production. TYK2 may drive beneficial or detrimental activities, which we explain based on the concepts of tumor immunoediting and the cancer-immunity cycle in the tumor microenvironment. Finally, we summarize current knowledge of TYK2 functions in mouse models of tumor surveillance. The biology and biochemistry of JAKs, TYK2-dependent cytokines and cytokine signaling in tumor surveillance are well covered in recent reviews and the oncogenic properties of TYK2 are reviewed in the recent Special Issue ‘Targeting STAT3 and STAT5 in Cancer’ of Cancers. View Full-Text
Keywords: tyrosine kinase 2; Janus kinase (JAK) family; STATs; immunoediting; cancer-immunity cycle; interferons; interleukins tyrosine kinase 2; Janus kinase (JAK) family; STATs; immunoediting; cancer-immunity cycle; interferons; interleukins
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Karjalainen, A.; Shoebridge, S.; Krunic, M.; Simonović, N.; Tebb, G.; Macho-Maschler, S.; Strobl, B.; Müller, M. TYK2 in Tumor Immunosurveillance. Cancers 2020, 12, 150.

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