Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Arginine restores T-cell ability to target cancer

23.11.2011
In many cases, tumors suppress a patient’s immune system in a way that keeps the cancer safe from immune system attack. This is particularly true for patients with glioblastoma, a primary brain tumor that carries a prognosis of only 12-15 months survival after diagnosis.

A study at the University of Colorado Cancer Center, recently published as a featured article in the journal Clinical Cancer Research, shows that treatment with the over-the-counter amino acid arginine may reactivate cancer-fighting T-cells in patients with glioblastoma, thus potentially allowing the immune system to help cleanse the body of cancer.

T-cells are the primary agent responsible for anti-tumor immune responses.

“If you take T-cells from patients with glioblastoma and stimulate them in the lab, they aren’t effective (in killing cancer cells),” says lead author Allen Waziri, MD, investigator at the CU Cancer Center, assistant professor of neurosurgery at the University of Colorado School of Medicine. “But when we add back arginine, we restore T-cell function.”

In part, function is restored through the activity of neutrophils – an ancient and nonspecific type of white blood cell that kills invaders. After responding to inflammation, neutrophils stop the ongoing immune response. It’s as if once they arrive, they consider the infection treated and so suppress any response that exceeds what is needed – a response that if left unchecked would lead to the destruction of healthy tissues.

Neutrophils stop the immune response by secreting an enzyme called arginase. And after they secrete arginase, commonly they die and are excreted by the body. However, in many glioblastoma patients, these neutrophils persist and continue to produce immune-suppressing arginase.

“Persistence of activated neutrophils and increased arginase in the circulation of glioblastoma patients is a fascinating phenomenon, particularly considering that under normal conditions, neutrophils are expected to have an average lifespan of just several hours after activation,” he says.

Waziri’s group has hypothesized that persistent arginase production from neutrophils suppresses the immune system and keeps cancers from becoming immune targets.

“From one perspective, it appears that glioblastoma is taking advantage of a simple, evolutionarily-ancient method for controlling out-of-control immunity to avoid the specific anti-tumor immune response,” Waziri says.

However, there is a step between increased arginase and immune system suppression, and this is where Waziri and colleagues intervene – arginase, in fact, deletes the common amino acid arginine.

T-cells are critically dependent on arginine for activation and function. Therefore, it’s not the increase in arginase per se that is responsible for blunting T-cell activity, but rather the resulting lack of arginine that suppresses the immune systems of glioblastoma patients, Waziri’s group found.

Waziri and colleagues at the CU Cancer Center recently started a phase 0 clinical trial in newly diagnosed glioblastoma patients to explore whether a week-long, high-dose course of arginine before cancer surgery can allow an immune system that previously missed cancer cells to recognize and attack them. Waziri and his team will look at the effect of arginine on patients’ immune systems as measured by T-cell function, immunological profile, and T-cell infiltration into resected tumor tissue.

“Our overall goal is to improve the efficacy of immunotherapy for glioblastoma,” he says. “It’s likely that this will require a two-stage approach, including stimulation of the immune system with something like a tumor vaccine while simultaneously targeting the suppressive effects of tumors on the immune system.”

With positive results from this initial trial, Waziri hopes to further explore whether longer courses of arginine could help reduce the recurrence of glioblastoma and potentially offer a new strategy for patients with this otherwise incurable disease.

Waziri credits seed grants he has received from the AMC Cancer Fund (a fundraising arm of the CU Cancer Center), he Cancer League of Colorado, and an American Cancer Society Institutional Research Grant for contributing to the preclinical work that has led to this exciting clinical trial.

Garth Sundem | EurekAlert!
Further information:
http://www.ucdenver.edu

Further reports about: Cancer T-cell amino acid cancer cells cell function immune response immune system

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>