Tyk2 is a key component of the immune system and has an important role in the defence against infections and cancer. Recent studies, however, have established that Tyk2 is strongly activated in certain types of cancer and that inhibition of its enzymatic activity stops cancer cell growth. A team from the Vetmeduni Vienna has now presented the first evidence that enzymatically inactive Tyk2 retains anti-cancer activity of immune cells in mice. Thus, Tyk2-inhibiting drugs do not impair the immune system’s fight against cancer. The results were published in the journal Oncoimmunology.
Tyrosine kinase 2 (Tyk2) is an enzyme involved in intracellular signalling and has an important role in activating the immune system. But enzymatically active Tyk2 can also promote excessive immune reactions and growth of certain cancer types.
Since several years, scientists are developing substances to specifically inhibit the kinase activity of Tyk2 for the treatment of inflammatory diseases and for potential use in cancer therapy. However, complications may occur: Tyk2 crucially contributes to the maturation and activation of natural killer (NK) cells.
NK cells form part of the innate immune system and are the first defence against virus infections and cancer. They recognise cancer cells and produce a series of proteins capable of destroying them. Inhibition of Tyk2 could therefore also weaken NK cells and block an important front of the body’s own defence against cancer.
First evidence of kinase-independent functions of Tyk2 in a living organism
A team of researchers led by Birgit Strobl, Mathias Müller and Veronika Sexl from the Institute of Animal Breeding and Genetics and the Institute of Pharmacology and Toxicology at the Vetmeduni Vienna investigated cancer growth in Tyk2 gene-targeted mice.
Tyk2-deficient mice were not able to control cancer growth. NK cells of these animals exhibited incomplete maturation and were unable to destroy cancer cells. Surprisingly, in mice whose Tyk2 was present but enzymatically inactivated, cancer growth was strongly suppressed and NK cells retained their ability to kill the cancer cells.
Project leader Birgit Strobl explains: “Until now, it was unknown that Tyk2 has effects within the whole organism that do not depend on its enzymatic activities. Without its kinase activity, it still drives NK cell maturation and boosts their activity. Here lies the key for cancer medicine. Drugs that inhibit the kinase activity of Tyk2 – and there are currently several of them in the testing phase – do not hamper the immune system in its work. These drugs are therefore even more promising for cancer therapy than previously thought.”
Research into proteins involved in the JAK/STAT signal pathway
The research forms part of a Special Research Programme (SFB) funded by FWF, the Austrian Science Fund. SFB F28 “Jak-Stat Signalling: From Basics to Disease” (http://www.jak-stat.at) involves a consortium of Viennese researchers with the participation of an international scientific network and aims to understand the function of JAKs (Janus kinases) and STATs (Signal Transducers and Activators of Transcription) in the context of inflammation, infection and cancer.
The article “In vivo tumor surveillance by NK cells requires TYK2 but not TYK2 kinase activity”, by
Michaela Prchal-Murphy, Agnieszka Witalisz-Siepracka, Karoline T. Bednarik, Eva Maria Putz, Dagmar Gotthardt, Katrin Meissl, Veronika Sexl, Mathias Müller and Birgit Strobl was published in the journal OncoImmunology. DOI:10.1080/2162402X.2015.1047579
About the University of Veterinary Medicine, Vienna
The University of Veterinary Medicine, Vienna in Austria is one of the leading academic and research institutions in the field of Veterinary Sciences in Europe. About 1,300 employees and 2,300 students work on the campus in the north of Vienna which also houses five university clinics and various research sites. Outside of Vienna the university operates Teaching and Research Farms. http://www.vetmeduni.ac.at
Prof. Mathias Müller
Institute of Animal Breeding and Genetics
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-5620
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-1151
Heike Hochhauser | idw - Informationsdienst Wissenschaft
'Lipid asymmetry' plays key role in activating immune cells
20.02.2018 | Biophysical Society
New printing technique uses cells and molecules to recreate biological structures
20.02.2018 | Queen Mary University of London
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
20.02.2018 | Life Sciences
20.02.2018 | Medical Engineering
20.02.2018 | Physics and Astronomy