Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New mechanism activates the immune system against tumour cells

17.06.2016

Only when cancer cells escape the surveillance by the immune system can a tumour grow. It is currently one challenge in cancer research to activate the body's natural defences to eliminate tumour cells. Veronika Sexl, head of the Institute of Pharmacology and Toxicology at the University of Veterinary Medicine Vienna, has now discovered with her team a surprising new function for the signalling molecule STAT1 in immune cells. This previously unknown feature could pave the way to a new therapeutic approach to immunological cancer therapy. The study results were published in the journal ‘OncoImmunology’.

The body's defences detect and eliminate not only pathogens but also tumour cells. Natural killer cells (NK-Cells) are specifically activated by chemical messengers, the Cytokines, to seek and destroy tumour cells. Veronika Sexl and her team from the Institute of Pharmacology and Toxicology at the Vetmeduni Vienna study the fundamentals of tumour surveillance by the immune system in animal models.


The new function of STAT1 can be a decisive factor for immune therapy of cancer says Veronika Sexl.

Michael Bernkopf/Vetmeduni Vienna

Cytokines trigger a signal cascade in NK cells recruiting them to tumour defence. An important player in this signalling process is the transcription factor STAT1. This molecule enters the cell nucleus to turn on genes required for the activation of NK cells. Until now it was assumed that NK cells are triggered by STAT1 mediated gene activation. However, Sexl and her team have now discovered that not gene transcription, but a previously unknown mechanism of STAT1 activates NK cells.

Genetics revealed unknown function of STAT1

The importance of the signalling molecule STAT1 for NK cells is revealed when it is absent. Without STAT1 tumour cells are inefficiently eliminated. The researchers wondered however, whether STAT1’s nuclear activity as transcriptional activator is essential for its function. "The activation of other genes is to date the only known and accepted function of STAT1. In order to show the actual role in the activation of NK cells we genetically removed this function, "said lead author Eva Putz.

To do so Sexl teamed up with researchers from the US and the University of Vienna, and generated mice with a modified STAT1. This altered STAT1 molecule is incapable of turning on genes by virtue of a single change in the protein sequence. Despite this modification, the NK cells were still surprisingly effective in eliminating tumour cells. "The activation of NK cells therefore depends on a previously unidentified STAT1 function, since the molecule without the known activity continues to function," explains Sexl.

The Immunological synapse harbours STAT1 for activation of NK cells

Using various experiments, Sexl and her co-workers could prove that STAT1 is capable of not only activating genes but also working directly with key players in the signalling process outside the nucleus. "A transcription factor performs its job in the cell nucleus, where the DNA is. But we observed STAT1 in activated NK cells not in the nucleus, but in regions close to the cell membrane, where NK cells and tumour cells meet" says Putz.

Apparently, STAT1 does not need to enter the nucleus in order to activate NK cells. Instead, STAT1 appears to be directly involved in the signalling of the NK cells, which upon activation eliminate the tumour cells. This represents a new function of STAT1, entirely independent of gene transcription.

"It will be an exciting challenge to explore this previously unknown function of STAT1 in tumour surveillance. Improving the mobilisation of NK cells in cancer patients is an intense area of research to make anti-tumour therapy more effective", concludes Sexl.

Service:
The article "Novel non-canonical role of STAT1 in natural killer cell cytotoxicity" by Eva Maria Putz, Andrea Majoros, Dagmar Gotthardt, Michaela Prchal-Murphy, Eva Maria Zebedin-Brandl, Daniela Alexandra Fux, Andreas Schlattl, Robert D. Schreiber, Sebastian Carotta, Mathias Müller, Christopher Gerner, Thomas Decker and Veronika Sexl published in the Journal OncoImmunology. doi:10.1080/2162402X.2016.1186314
http://www.tandfonline.com/doi/abs/10.1080/2162402X.2016.1186314?journalCode=kon...

About the University of Veterinary Medicine Vienna
The University of Veterinary Medicine Vienna (Vetmeduni Vienna) is one of the leading veterinary, academic and research facilities in Europe. Its main focus is on the research fields of animal health, food safety, animal husbandry and animal welfare as well as biomedical fundamentals. The Vetmeduni Vienna has 1,300 employees and is currently training 2,300 students. The campus in Floridsdorf, Vienna has five university hospitals and numerous research institutions at its disposal. Two research institutes at Wilhelminenberg, Vienna and a Teaching and Research in Lower Austria also belong to the Vetmeduni Vienna. http://www.vetmeduni.ac.at

Scientific contact:
Veronika Sexl
Institute of Pharmacology and Toxikology
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-2910
veronika.sexl@vetmeduni.ac.at

Released by:
Georg Mair
Science Communication / Corporate Communications
University of Veterinary Medicine Vienna (Vetmeduni Vienna)
T +43 1 25077-1165
georg.mair@vetmeduni.ac.at

Weitere Informationen:

http://www.vetmeduni.ac.at/en/infoservice/presseinformation/presseinformationen-...

Mag.rer.nat Georg Mair | Veterinärmedizinische Universität Wien

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>