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 Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>