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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>