Arginine restores T-cell ability to target cancer
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.
Provided by University of Colorado Denver
- Clinical trial evaluating brain cancer vaccine is underway Oct 19, 2007 | not rated yet | 0
- Immunogene therapy combined with standard treatment is safe for patients with brain tumors Aug 15, 2011 | not rated yet | 0
- Cancer stem cells suppress immune response against brain tumor Jan 15, 2010 | not rated yet | 0
- Common virus may help doctors treat deadly brain tumors Oct 22, 2007 | not rated yet | 0
- Study: Tumors inhibit immune system May 29, 2006 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
15 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Cancer 3 hours ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
Cancer 4 hours ago | not rated yet | 0
A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...
Cancer 5 hours ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 6 hours ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 8 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
10 hours ago | 4 / 5 (4) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
8 hours ago | 4.8 / 5 (6) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
4 hours ago | 5 / 5 (1) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
5 hours ago | 5 / 5 (3) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
10 hours ago | 4.8 / 5 (4) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
6 hours ago | not rated yet | 0 |