One way tumors fly under the radar of the immune system is by using IDO, an enzyme used by fetuses to help avoid rejection, to recruit powerful regulatory T cells that turn down the immune response, researchers say.
It was known tumors assemble a protective barrier of regulatory T cells, or Tregs, but how they are such able recruiters was an unknown, says Dr. David Munn, pediatric hematologist/oncologist at the Medical College of Georgia Cancer Center.
People have been very interested in how the tumor gets so many of these cells and how they get activated so they tend to be very aggressive, more suppressive in the tumor than they appear to be elsewhere in the body, Dr. Munn says of Tregs, major players in preventing autoimmune diseases such as arthritis and type 1 diabetes, where the immune system attacks body tissue.
Research published online Aug. 16 in The Journal of Clinical Investigation shows IDO, which seems to play a powerful role in tumor survival despite the relatively few number of cells in the tumors draining lymph nodes, directly activates existing Tregs which become strongly suppressive within a day. The number doesnt change a lot, but their activation state changes hugely, says Dr. Munn, corresponding author.
Studies in a tumor animal model show this rapid conversion occurs only in lymph nodes connected to tumors.
The findings further define a tumors survival strategy of first recruiting IDO, which helps recruit Tregs. Tregs then up-regulate the PD-L1/PD-L2 pathway, which has been shown to play an important role in the immune suppression caused by AIDS.
For the first time it creates a link between IDO, regulatory T cells and this novel pathway we dont know much about, says Dr. Munn. Interestingly its a link that appears to come full circle because, as researchers at the University of Perugia in Italy showed in 2003, in the test tube at least, Tregs also help recruit more IDO.
|Contact: Toni Baker|
Medical College of Georgia