Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Traitorous immune cells promote sudden ovarian cancer progression

21.02.2012
First model of aggressive ovarian cancer demonstrates immune system's active role in tumor progression

Aggressive ovarian tumors begin as malignant cells kept in check by the immune system until, suddenly and unpredictably, they explode into metastatic cancer. New findings from scientists at The Wistar Institute demonstrate that ovarian tumors don't necessarily break "free" of the immune system, rather dendritic cells of the immune system seem to actively support the tumor's escape. The researchers show that it might be possible to restore the immune system by targeting a patient's own dendritic cells.

"Our model shows where the cancer is kept in check for relatively long periods, but once they become noticeable, tumors grow exponentially," said José R. Conejo-Garcia, M.D., Ph.D., an associate professor at Wistar and leader of the Tumor Microenvironment and Metastasis Program of Wistar's Cancer Center. "More importantly, we show that by depleting these dendritic cells of the immune system, we can reverse the effect, once again allowing our immune system to recognize the ovarian tumors."

Their findings, presented in the March issue of the Journal of Experimental Medicine, available online now, represent the first successful attempt to model the tumor microenvironment of human ovarian cancer in a mouse model of the disease. In essence, the model replicates the inflammatory surroundings that ovarian tumors experience in humans. The more accurate model provides a better tool for researchers to understand, prevent, and treat tumors.

"Our system uses oncogene-driven tumors that are spontaneously antigenic, thus avoiding the use of artificial foreign antigens that do not accurately replicate what drives anti-tumor immune responses in humans," Conejo-Garcia said.

Ovarian cancer remains one of the most deadly forms of cancer in women. According to the National Cancer Institute, 21,990 women will be diagnosed with ovarian cancer, and 15,460 women will die of the disease this year Because early-stage ovarian cancer does not often exhibit noticeable symptoms, many women are not diagnosed until the cancer is at a later stage, when it is most difficult to treat.

"While we have seen an increase in survival rates for most cancers over the last 40 years, ovarian cancer survival has only improved slightly since the 1970's," Conejo-Garcia said. "We created our ovarian cancer model to get a better understanding of how these tumors acquire such aggressive characteristics and evade the immune system."

According to Conejo-Garcia, their model demonstrates how a localized ovarian tumor flares into an aggressive metastatic disease.

"You can see where, if one ovary is cancerous, it is almost unrecognizable until an instantaneous moment, when it explodes into exponential growth," Conejo-Garcia said. "The key to this moment, our evidence suggests, is in the phenotypic changes taking place in the dendritic cells that are part of the tumor microenvironment."

In healthy tissue, dendritic cells function as sort of alarm system to alert the adaptive part of the immune system to potential threats. They work as antigen-presenting cells, offering foreign or disease-causing molecules (called antigen) to the white blood cells that can then respond to an infection or, in this case, tumorous growths. Amid the ovarian cancer microenvironment, dendritic cells also induce the immune system to attack tumor cells and inhibit their growth.

Until, that is, dendritic cells seem to switch sides.

"We see a change in the dendritic cells themselves, which allows tumors to progress to terminal disease in a very short time," Conejo-Garcia said. "Interestingly, the tumors themselves are still immunogenic—they could still otherwise elicit an immune response—it is just that the dendritic cells are actively suppressing the involvement of other anti-tumor immune cells; primarily T cells."

Conejo-Garcia and his colleagues believe that their findings offer a twist on the emerging theory of "cancer immunoeditting." The immunoeditting hypothesis suggests that the immune system actively "edits" tumor cells to eliminate antigens that are recognized by immune cells, keeping the cancer at bay before it becomes symptomatic. All symptomatic tumors, therefore, represent a failure of the immune system, where tumors lose their immunogenicity—their ability to trigger and be recognized by our immune system.

The researchers found that that depleting dendritic cells early on accelerating tumor expansion, while removing dendritic cells later on actually delayed the tumor's progression. According to Conejo-Garcia, their findings suggest it is a change in the immune system itself, specifically the dendritic cells, and not primarily any loss of immunogenicity on the part of the tumor.

"It is almost as if anti-tumor T cells become exhausted, they can no longer keep up the effort," Conejo-Garcia said. "Still, our findings suggest that the enduring activity of these T cells would allow us to control metastatic ovarian cancer by targeting the dendritic cells that actively prevent their anti-tumor functions."

In fact, Conejo-Garcia and his colleagues have already developed a strategy to reprogram traitorous dendritic cells. In a an upcoming edition of the journal Cancer Research, available online now, the researchers demonstrate how synthetic RNA molecules can be used to win back the allegiance of dendritic cells and restore their ability to stimulate tumor suppression.

Funding for this research was provided through grants from the National Cancer Institute and the Department of Defense.

The lead author of the study is Uciane K. Scarlett, Ph.D., a staff scientist in the Conejo-Garcia laboratory. Wistar co-authors also include Melanie R. Rutkowski, Ph.D. and Ximena Escovar-Fadul. Co-authors from Darmouth Medical School include Adam M. Rauwerdink, Ph.D., Jennifer Fields, Jason Baird, Juan R. Cubillos-Ruiz, Ph.D. (currently at Harvard University), Ana C. Jacobs, Jorge L. Gonzalez, M.D., John Weaver, Ph.D., and Steven Fiering, Ph.D.

Greg Lester | EurekAlert!
Further information:
http://www.wistar.org

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>