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

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

Join For Free

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 3,400+ scientific posters on ePosters
  • More than 4,900+ 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 TechnologyNetworks.com 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

Migration Creates Cancer Cell Vulnerabilities
Scientists found that migration can damage cancer cells’ nuclei and DNA, requiring repairs for their survival. The results may open new avenues for targeting metastatic cancer.
Wednesday, April 13, 2016
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
NASA's DNA Sequencing in Space is a Success
DNA has been sequenced in space for the first time ever for the Biomolecule Sequencer investigation, using the MinION sequencing device.
Lab-on-a-Stick: Miniaturised Clinical Testing For Fast Detection Of Antibiotic Resistance
A portable power-free test for the rapid detection of bacterial resistance to antibiotics has been developed by academics at Loughborough University and the University of Reading.
Breast Cancer Cells Found To Switch Molecular Characteristics
Spontaneous interconversion between HER2-positive and HER2-negative states could contribute to progression, treatment resistance in breast cancer.
Measuring Chemistry on a Chip
Researchers developing chemical sensor chip for sample analysis in a lab or monitoring air and water quality in the field.
Automating Genetic Analysis
Researchers are looking to have computers help perform genetic analysis when scientists study a patient's genome to diagnose a disease.
DNA Condensation on a Chip
Carriers of genetic information packed together on a biochip like in nature.
Microchip Tech Improves Nanomaterial Safety Screening
Platform developed at UCLA uses lab-on-a-chip technology to predict how hazardous engineered nanomaterials might be.
Four Key Dynamics Driving Effective Outsourcing Decision Making for Lab Automation OEMs
Laboratory automation device manufacturers need to stay flexible in their outsourcing strategies because their make-versus-buy decisions may change over time.
How Cloud Connectivity Can Combat the Reproducibility Crisis
This infographic explains the reproducibility crisis, and how cloud connectivity can help overcome this problem.
'Fixing' Blood Vessel Cells To Diagnose Blood Clotting Disorders
A novel microfluidic device detects how endothelial cells that line vessels contribute to hemostasis.
Scroll Up
Scroll Down
SELECTBIO

SELECTBIO Market Reports
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
3,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!