Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune system 'escape hatch' gives cancer cells traction

18.07.2007
Discovery explains why anticancer vaccines mostly fail

Scientists at Johns Hopkins and elsewhere say they have mapped out an escape route that cancers use to evade the body’s immune system, allowing the disease to spread unchecked.

In a report published in the July 1 issue of the journal Nature Medicine, the Hopkins team, along with researchers from Florida and Nebraska, describe how myeloid-derived suppressor cells (MDSCs), which normally keep the immune system in check and prevent it from attacking otherwise healthy tissue, can suppress the anti-tumor response to cancer.

These suppressor cells block other immune system cells, CD8 “killer” T cells, from binding with proteins that identify the foreign antigens on the surface of unhealthy cancer cells, marking them for destruction, the team reports.

... more about:
»MDSC »T cells »T-cell »Vaccine »escape »tolerance

The good news, they say, is that their experiments also suggest that the chain reactions in T-cell tolerance are reversible, raising the possibility of vaccine and drug therapies that break through the blocked immune system.

Previous research had confirmed that MDSCs, produced in the bone marrow, were attracted to tumors, but until now, scientists had not identified exactly how the cells inhibit the immune system’s ability to mount an attack.

By explaining some of the precise biological workings of MDSCs in cancer the team’s findings suggest why experimental cancer vaccines have to date been plagued by T-cell tolerance, a weakened rather than strengthened immune response, says Jonathan Schneck, M.D., Ph.D., one of the study’s authors.

“Our findings also open up a new door in drug and vaccine development that we never knew existed and provide another opportunity for drug development into autoimmune diseases, where the immune system is in overdrive and needs to be slowed down,” says Schneck, a professor of medicine, pathology and oncology at The Johns Hopkins University School of Medicine and its Kimmel Cancer Center.

The team’s latest report built on research initially conducted at the University of South Florida, where researchers analyzed blood samples and lymph tissue from healthy mice injected with MDSCs and found that T-cell levels remained the same, indicating that MDSCs did not destroy the immune response but apparently altered how the T cells behaved.

Using chemical tests in which individual tumor cells can be tagged with a fluorescent dye that allows them to glow when they are not bound to T cells, Florida researchers measured the immune response in mice to various foreign proteins, with and without injections of MDSCs. They found an 80 percent suppression of the immune response in the presence of MDSCs, confirming that the suppressor cells were inactivating the T cells.

The Florida team then turned to Schneck, who in 1993 developed several novel proteins to test how various antigens, such as those on cancer cells, specifically latch on to T cells.

Researchers then began experiments to determine if the MDSC T-cell interference was simply genetic or had some biochemical explanation, testing a half-dozen major reactions known to occur during infection to see if any set path was particularly active during interference.

In tissue tests from tumor-filled mice bred to lack a biochemical reaction, the scientists found that one specific pathway, the reactive-oxygen species, or ROS pathway, stood out, because when inactivated, T-cell tolerance did not develop. Researchers were surprised when subsequent tests showed that ROS actually modified the T cells, altering their structure so they could no longer bind to tumor-cell antigens.

When a known byproduct of ROS, the chemical peroxynitriate, was neutralized, T-cell tolerance failed to develop in test tube studies, pinning down peroxynitrate as the culprit prohibiting immune cell binding to and marking of “foreign” tumor cells.

“Peroxynitrate activity is the escape hatch, and now that we have identified it, we can try to cut it off before T-cell tolerance develops, or you can reverse it,” says Schneck.

Plans are underway to investigate the binding receptors of MDCSs and different anticancer drugs for their ability to lower levels of MDSCs and to explore the role of MDSCs in suppressing the immune response to stress, bacterial and viral infections, organ transplantation and autoimmune diseases. Their goal, researchers say, is to find some means of accelerating or slowing down T-cell activity gone awry.

David March | EurekAlert!
Further information:
http://www.jhmi.edu

Further reports about: MDSC T cells T-cell Vaccine escape tolerance

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>