Corporate Banner
Satellite Banner
Automation & Microfluidics
Scientific Community
Become a Member | Sign in
Home>News>This Article

NIH Study Identifies Gene that Suppresses Cell's Immune Activation

Published: Wednesday, April 06, 2011
Last Updated: Wednesday, April 06, 2011
Bookmark and Share
FOXO3 gene suppresses activation of cells related to immunity and thus leads to a reduced immune response against a growing cancer.

A new study of prostate tumors has shown that a gene, FOXO3, suppresses activation of cells related to immunity and thus leads to a reduced immune response against a growing cancer. One of the main problems in treating cancer by vaccine or immunotherapy is that tumors often evade the body's immune response - and one of their tricks is to create an environment where immunity is inhibited or suppressed.

By identifying a gene that makes immune cells suppressive, the researchers may have found a new target for enhancing immune responses to cancer tumor cells. The study, by scientists from the National Cancer Institute (NCI), part of the National Institutes of Health, appeared online March 23, 2011, in the Journal of Clinical Investigation, and in print April 1, 2011.

The cells isolated and examined in this study were dendritic cells. These cells normally initiate an immune response to disease by presenting a foreign protein (or antigen) in a way that it is recognized by an invader-killing T cell. In tumor-associated dendritic cells, however, this stimulating immune response is often suppressed.

To overcome the problem associated with tumor-associated dendritic cells, Arthur A. Hurwitz, Ph.D., head of the Tumor Immunity and Tolerance Section, NCI, and postdoctoral fellow Stephanie K. Watkins, Ph.D., conducted a series of experiments aimed at enhancing immunity to tumors. As a result, they discovered that prostate tumors from mice contained a population of dendritic cells that express FOXO3 at high levels.

These dendritic cells no longer activated T cells. Instead, they muted the immune response, which caused the T cells to become tolerant of tumor cell antigens, to lose their ability to target and kill tumor cells, and even to suppress the activity of other T cells.

Under certain conditions, elimination of the suppressive dendritic cells led to reduced tumor size. The findings made in mice then led the research team to examine human prostate tumors in the lab where they found similar dendritic cells with high FOX03 levels.

In past studies, Hurwitz and his colleagues worked to identify how tumors evade recognition by the immune system. Their results showed that, in the same mouse model of prostate cancer, T cells become tolerant upon entering a tumor and acquire the ability to suppress other T cells.

In this study, the scientists demonstrated not only that dendritic cells isolated from tumors were poor at initiating immune responses, but also that these cells were responsible for inducing T cell tolerance and converting them to suppressor T cells.

Using microarray technology, a technique that allows scientists to examine the expression of thousands of genes simultaneously, they compared the genes expressed by the tumor-associated dendritic cells to those expressed by dendritic cells in normal tissue.

Among the genes that were overexpressed in the tumor-associated dendritic cells, FOXO3 was an appealing candidate for an immune modulator because it was known to be a regulator associated with dendritic cell function.

When FOXO3 gene expression was silenced in the tumor-associated dendritic cells, the scientists found that these cells no longer had an immune suppressive function but rather initiated appropriate immune responses.

"Our research suggests that it may be possible to boost immune responses to tumors and prevent immune suppression if we target FOXO3, either directly or with prostate and other cancer vaccines. This might be achieved by using small molecule drugs or peptides that target FOXO3 in dendritic cells or by silencing FOXO3 expression in dendritic cell vaccines that already exist, making them more potent," said Hurwitz. "We believe this finding could also be applied to treating autoimmune diseases, where therapies aimed at inducing immune suppression may benefit from enforcing expression of FOXO3."

This work has led to the submission of a patent application by the NIH on behalf of Hurwitz and Watkins to target FOXO3 as a way to boost immune responses in cancer and to silence excessive immune responses in autoimmune diseases. While waiting for patent approval, the scientists will study how tumors, or the tumor microenvironment, induce FOXO3 expression as well as how FOXO3 induces this suppressive activity.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Futuristic Brain Probe Allows for Wireless Control of Neurons
NIH-funded scientists developed an ultra-thin, minimally invasive device for controlling brain cells with drugs and light.
Saturday, July 18, 2015
NIH Funds Nine Antimicrobial Resistance Diagnostics Projects
Investigators to develop tools to detect hospital-associated pathogens.
Friday, April 10, 2015
NIH Funds Next Phase of Tissue Chip for Drug Screening Program
Scientists will integrate chips mimicking human organ functions into full body system to evaluate drugs.
Thursday, September 25, 2014
NIH Awards $14.5M for DNA Sequencing Techniques
For the past several years, nanopore research has been an important focus of the program’s grants.
Tuesday, August 05, 2014
NIH Funds Development of Tissue Chips to Help Predict Drug Safety
DARPA and FDA to collaborate on therapeutic development initiative.
Wednesday, July 25, 2012
NIH, DARPA and FDA Collaborate to Develop Cutting-Edge Technologies to Predict Drug Safety
The collaboration will develop a chip to screen for safe and effective drugs far more swiftly and efficiently than current methods, and before they are tested in humans.
Monday, September 19, 2011
Scientific News
Discovery Provides New Opportunities for Chips
Scientists at the University of Twente's MESA+ research institute have developed a new manufacturing method to create three-dimensional nanostructures.
Penn Engineering Team Showcases ‘Eye-on-a-Chip’ Technology
These small plastic chips contain microfluidic channels, carefully designed so that human cells can grow in them in a way that simulates the three-dimensional environments they would normally inhabit in the body.
Miniaturizable Magnetic Resonance
Microscopic gem the key to new development in magnetic lab-on-a-chip technology.
Education and Expense: The Barriers to Mass Spectrometry in Clinical Laboratories?
Here we examine the perceived barriers to mass spec in clinical laboratories and explore the possible drivers behind the recent shift in uptake of the technology in clinical settings.
Chip-Based Technology Enables Reliable Direct Detection of Ebola Virus
Hybrid device integrates a microfluidic chip for sample preparation and an optofluidic chip for optical detection of individual molecules of viral RNA.
Stem Cell Research Hints at Evolution of Human Brain
Researchers at UC San Francisco have succeeded in mapping the genetic signature of a unique group of stem cells in the human brain that seem to generate most of the neurons in our massive cerebral cortex.
Developing a Breathalyzer-Type Low Blood Sugar Warning Device For Diabetes
A multidisciplinary team of researchers at Indiana University-Purdue University Indianapolis has been awarded a $738,000 National Science Foundation grant to develop a breathalyzer-type device to detect the onset of hypoglycemia, or low blood sugar episodes, in people with diabetes.
Smartphone App to Monitor Serious Blood Disorder
A researcher from Florida Atlantic University has come up with a unique way to monitor sickle cell disease -- a serious blood disorder -- using a smart phone.
Preventing Crystallization to Improve Drug Efficiency
Esther Amstad and an international team of researchers have developed a method to increase the solubility of poorly soluble substances, such as many of the newly developed drugs.
‘Lab-on-a-Chip’ Technology Cuts Costs of Lab Tests
With ability to analyze minuscule amounts of fluid, Rutgers breakthrough could also promote central nervous system and joint research.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos