The human immune system uses natural killer (NK) cells as a weapon against cancer and virus-infected cells. A higher activity of the NK cells corresponds directly to a higher effectiveness in fighting tumors. Researchers at Vetmeduni Vienna, in a study published in Cancer Immunology Research, have now shown that it is possible to enhance NK cell activity even further by deleting the CDK8 gene. Until now, CDK8 is known to have an important role in the formation of tumors, where its activity is often amplified. Inhibiting CDK8 activity is the object of several current studies.
Decades have been spent investigating how cancer cells manage to reproduce while evading the control of the immune system. So-called immunotherapies are currently being researched as a way to strengthen the body’s immune system response against tumors. Researchers from the Institute of Pharmacology and Toxicology at Vetmeduni Vienna, with first author Agnieszka Witalisz-Siepracka, have made important progress in this direction.
They show how the activity of NK cells against tumors can be enhanced through the deletion of the CDK8 gene. CDK8 is a cyclin-dependent kinase that controls several vital functions within human cells. When CDK8 is hyperactive, it can result in cell transformation.
In their study in Cancer Immunology Research, the researchers focused on the tumor surveillance system. They were able to show that CDK8 plays a special part in NK cells, where it suppresses their activity. By deleting CDK8, the research team succeeded in significantly restricting tumor growth in mice. Witalisz-Siepracka draws the following conclusions: “Deletion of CDK8 led to increased activation of the NK cells. You could say they became ‘armed’. Their ability to kill grew and the tumor shrank.”
This study builds on a previously published study by the same research group in which the researchers had postulated that CDK8 has a pivotal role in the killing activity of NK cells in cell culture models. Now they have gone an important step further by transferring their knowledge to tumor growth in vivo. “This had not been confirmed in a living organism before,” says Witalisz-Siepracka. “Because there are currently a number of preclinical studies on the development of CDK8 inhibitors, we wanted to determine the effects CDK8 deletion would have on the NK cells.”
“Arming” an immunological weapon through the deletion of CDK8
The researchers obtained their research results by using specially designed mice with selective deletion of CDK8 in NK cells. “We need a new class of CDK8 inhibitors for immunotherapy. Such an inhibitor would have to trigger the breakdown of the entire CDK8 protein. In addition to the tumor cell-intrinsic effect, the immune system would also be activated to fight the tumor cells. The result would be a double blow against the cancer cells.” Senior author Veronika Sexl summarizes the findings: “Degradation of CDK8 could be a promising way to fight tumors using the body’s own arsenal.”
The article “NK Cell-Specific CDK8 Deletion Enhances Antitumor Responses” by Agnieszka Witalisz-Siepracka, Dagmar Gotthardt, Michaela Prchal-Murphy, Zrinka Didara, Ingeborg Menzl, Daniela Prinz, Leo Edlinger, Eva Maria Putz and Veronika Sexl was published in Cancer Immunology Research.
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. The Vetmeduni Vienna plays in the global top league: in 2017, it occupies the excellent place 8 in the world-wide Shanghai University veterinary in the subject "Veterinary Science". http://www.vetmeduni.ac.at
Institute of Pharmacology and Toxikology
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-2900
Science Communication / Corporate Communications
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-1165
Mag.rer.nat. Georg Mair | idw - Informationsdienst Wissenschaft
Elusive compounds of greenhouse gas isolated by Warwick chemists
18.09.2019 | University of Warwick
Study gives clues to the origin of Huntington's disease, and a new way to find drugs
18.09.2019 | Rockefeller University
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Hamburg and the European Molecular Biology Laboratory (EMBL) outstation in the city have developed a new method to watch biomolecules at work. This method dramatically simplifies starting enzymatic reactions by mixing a cocktail of small amounts of liquids with protein crystals. Determination of the protein structures at different times after mixing can be assembled into a time-lapse sequence that shows the molecular foundations of biology.
The functions of biomolecules are determined by their motions and structural changes. Yet it is a formidable challenge to understand these dynamic motions.
At the International Symposium on Automotive Lighting 2019 (ISAL) in Darmstadt from September 23 to 25, 2019, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, a provider of research and development services in the field of organic electronics, will present OLED light strips of any length with additional functionalities for the first time at booth no. 37.
Almost everyone is familiar with light strips for interior design. LED strips are available by the metre in DIY stores around the corner and are just as often...
Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.
This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.
Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.
If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...
10.09.2019 | Event News
04.09.2019 | Event News
29.08.2019 | Event News
18.09.2019 | Innovative Products
18.09.2019 | Physics and Astronomy
18.09.2019 | Materials Sciences