Natural killer (NK) cells are an innate weapon against cancer and virus-infected cells. The higher the NK cell activity, the higher its effect against a tumour. Researchers at Vetmeduni Vienna have now shown that the NK cell cytotoxic activity can be increased even further if the cdk8 gene is removed in these cells. This translates into an improved NK cell–mediated tumour surveillance in vivo in three independent cancer models.

For decades, researchers have been interested in how cancer cells proliferate despite the action of the immune system. In order to increase the activity of the body's immune system against the tumour, researchers at the Institute for Pharmacology and Toxicology at Vetmeduni Vienna have now shown a way to increase the killing activity of NK cells against tumour cells. In order to achieve this, the NK cells were depleted from the cdk8 gene, which codes for the cyclin-dependent kinase 8 (CDK8). This led to the significant blocking of tumour growth in mouse models. Agnieszka Witalisz-Siepracka, first author of this study, explains that: “Due to the loss of CDK8, the NK cells were activated more intensely and their ability to kill increased; therefore, the tumour shrank."

These results define a suppressive effect of CDK8 on NK-cell activity and open the exciting possibility of targeting CDK8 in cancer patients to enhance NK-cell responses against tumour cells, thus using the body’s own weapons. Such inhibitors are already being developed in a number of pre-clinical stage studies.

Publication in Cancer Immunology Research

Agnieszka Witalisz-Siepracka, Dagmar Gotthardt, Michaela Prchal-Murphy, Zrinka Didara, Ingeborg Menzl, Daniela Prinz, Leo Edlinger, Eva Maria Putz and Veronika Sexl

https://cancerimmunolres.aacrjournals.org/content/6/4/458.long

Doi: 10.1158/2326-6066.CIR-17-0183

Christian Stockmann,
Universität Zürich,
Medizinische Fakultät,
Anatomisches Institut

Title: Immune cell-driven angiogenesis affecting organ remodelling during tissue hypoxia

Christian Stockmann’s research group aims to decipher how immune cell-driven angiogenesis affects organ remodeling during tissue hypoxia and also on the role of hypoxia-inducible factors in distinct immune cell subsets and their impact on tissue fibrosis after injury as well as on the progression of malignant tumors.

http://www.anatomy.uzh.ch/en/research/stockmann.html

The invitation only meeting on May 6-9, 2018 boasts an outstanding scientific programme and will take place in a beautiful location and inspiring atmosphere. We have invited international experts to complement the scientific programme of the two SFBs, including: Jacqueline Bromberg, New York; Gerard Evan, Cambridge; Thomas Graf, Barcelona; Nancy Hynes, Basel; Shai Izraeli, Tel Aviv; David Levy, New York; A. Tom Look, Harvard;  Tak Mak, Toronto

A cooperation of Ludwig Boltzmann Institute for Cancer Research, Ludwig Boltzmann Cluster Oncology, SFB-F47, and SFB-F61

Figure: The meeting will be held at Seggau Castle in Styria, close to the city of Leibnitz

Acute myeloid leukaemia (AML) is the most common type of acute cancer of the blood and bone marrow in adults. This type of cancer usually progresses quickly and only 26 percent of the patients survive longer than 5 years as resistance against established treatments arises. The most common molecular cause is FLT3 mutations, which result in hyper-activation of STAT5. An international consortium of researchers cofounded by SFB-F61 now report on an early preclinical development to target STAT5 directly, which cooperates well with existing therapies.

Publication in Leukemia:

Bettina Wingelhofer, Barbara Maurer, Elizabeth C. Heyes, Abbarna C. Cumaraswamy, Angelika Berger-Becvar, Elvin D. de Araujo, Anna Orlova, Patricia Freund, Frank Ruge, Jisung Park, Gary Tin, Siawash Ahmar, Charles-Hugues Lardeau, Irina Sadovnik, Dávid Bajusz, György Miklós Keserű, Florian Grebien, Stefan Kubicek, Peter Valent, Patrick T. Gunning and Richard Moriggl,

Pharmacologic inhibition of STAT5 in acute myeloid leukemia, Leukemia (2018), doi:10.1038/s41375-017-0005-9

Figure: Schematic representation of the STAT5 Inhibitor mapped onto the SH2-domain of STAT5

Acute myeloid leukemia (AML) is the most common form of acute cancer in the blood and bone marrow in adults. The most common molecular cause are mutations in the Flt3 gene, which activate the signal transmitter and transcription factor STAT5. A new strategy has now been described to directly inhibit STAT5 with a novel compound, in the scientific journal Leukemia.

AML, as one of the most devastating white blood cells disorders, is usually very aggressive and despite considerable progress in therapeutic approaches only 26% of patients survive for more than 5 years because of resistance to treatments. This type of leukemia is often caused by mutations that overactivate intracellular signalling or gene transcription. Mutations in the receptor FLT3, which represent 30% of the driver mutations in AML, activate STAT5, an important transcription factor that is required for the transformation of blood cells. New treatment strategies to inhibit STAT5 are needed to improve the survival of patients with this disease.

Previous attempts to inhibit STAT5 transcription factors often failed due to the effectiveness or lack of specificity. Now, an international consortium of researchers from Austria, Canada and Hungary, led by Richard Moriggl, reports a new compound that directly binds and selectively inhibits STAT5. The researchers could target STAT5 at the SH2 domain, which is essential for its activity, and discovered that the new inhibitor efficiently blocks the pathological levels of STAT5 activity in AML. It does so by disrupting STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription, which leads to a substantial impair in the proliferation and clonogenic growth of human AML cells in vitro and in vivo. Collaboration with a pharmaceutical company will now be required to further develop this new class of compound to make it suitable for a clinical trial.

Publication in Leukemia

 Bettina Wingelhofer, Barbara Maurer, Elizabeth C. Heyes, Abbarna A. Cumaraswamy, Angelika Berger-Becvar, Elvin D. de Araujo, Anna Orlova, Patricia Freund, Frank Ruge, Jisung Park, Gary Tin, Siawash Ahmar, Charles-Hugues Lardeau, Irina Sadovnik, Dávid Bajusz, György Miklós Keserű, Florian Grebien, Stefan Kubicek, Peter Valent, Patrick T. Gunning and Richard Moriggl

Doi: https://doi.org/10.1038/s41375-017-0005-9

Two PhD students from the Institute for Animal Breeding and Genetics of the Vetmeduni Vienna were awarded session prizes at the 2017 annual conference of the Austrian Society for Allergology and Immunology (ÖGAI). Natalija Simonovic won a prize for her oral presentation “Tyrosine kinase 2 (TYK2) regulates NK cell function by cell-intrinsic and –extrinsic mechanisms” and Andrea Pölzl received the prize for the poster "Tyrosine kinase 2 (TYK2) enables sustained IL-1beta production through the upregulation of caspase-11 during endotoxemia".

The annual meeting of the ÖGAI, which took place in Vienna from November 23th to 25th 2017, focused on Immunotherapy. In six independent sessions, different scientific contributions and perspectives on this topic were presented and discussed in lectures and poster presentations by national and international researchers. The ÖGAI was founded in 1970 and is a platform for researchers in Austria who are scientifically active in this scientific field. 

On December 13th 2017, the Rectorate awarded the most successful researchers of the year with the internal science awards of the Vetmeduni Vienna. Veronika Sexl (Institute of Pharmacology and Toxicology) and Mathias Müller (Institute of Animal Breeding and Genetics) won the prize for “major project” for successfully assuring grants from the European Research Council (ERC) and the FWF Special Research Program, respectively.

Each year, the Rectorate of Vetmeduni Vienna honors scientists for “invention of the year”, “most cited scientist”, “highest third-party funding” and the "major project of the year" with internal science prizes. The prizes were awarded according to the different career stage, in clinical and non-clinical categories, as well as in two age groups (younger than 35 years and older than 35 years). Pictures of the event can be found here.

On November 30th 2017, Veronika Sexl, Head of the Institute for Pharmacology and Toxicology at the Vetmeduni Vienna, was awarded the City of Vienna Prize (Preis Stadt Wien) in the Medical Sciences category for her life's work. Veronika Sexl was honored in the field of medicine for her outstanding performance during her career. In this video, the researcher talks about her career and what science is for her.

The City of Vienna Prizes are awarded every year in a wide variety of areas. An independent jury of experts decides annually on the awarding of prizes, which are endowed with 8,000 euros each. The City Councillor for Culture, Andreas Mailath-Pokorny, awarded the City of Vienna 2017 Prizes in eight categories. The full list of awardees can be found here.

Dagmar Gotthardt was awarded the Ursula and Fritz Melchers Prize for best dissertation at annual conference of The Austrian Society for Allergology and Immunology (ÖGAI) on November 24th 2017. She completed her PhD in 2016 at the Institute for Pharmacology and Toxicology at Vetmeduni Vienna with the PhD dissertation "The Role of STAT3 and STAT5 in murine Natural Killer Cells". This prize sums to others that the researcher received during her studies.

Dagmar was able to show that NK cells not only kill tumour cells, but can also promote tumour growth in certain circumstances. She identified STAT5 as the central switch in this decision. Dagmar was able to contribute to a total of 14 publications; she was the first author in 4 publications. The ÖGAI dissertation prizes are awarded for PhD dissertations with a scientifically outstanding content in the field of allergology or immunology. The first prize is donated by Ursula and Fritz Melchers in the amount of 1,500€.

Two students from Vetmeduni Vienna were awarded presentation prizes at the joint symposium of the PhD programs “Inflammation and Immunity” and “Molecular, Cellular and Clinical Allergology”. This was the second edition of this joint symposium, this year with the title "Together one step further". It happened on September 25th and 26th 2017 at the Medical University of Vienna.

Daniela Prinz from the Institute of Pharmacology and Toxicology won the best lecture by the students for the oral presentation "NKG2D: friend or foe in NK cell mediated tumour surveillance". Ana Puga from the Institute of Animal Breeding and Genetics won the best poster award with the work "The role of STAT1 isoforms in Th cell differentiation and CD4+ T cell-mediated diseases".