Tumors May Promote Inflammation to Evade Detection
A new study suggests that inflammation triggered by a protein found in many human tumors may help the tumors grow and avoid attacks by the immune system.
The protein, interleukin (IL)-23, represents an important link between inflammation and cancer, the researchers say. And it may help explain why cancers tend to occur in tissues that have been damaged by chronic inflammation.
In the study, researchers from Schering-Plough Biopharma in California found that IL-23 has an increased presence in many types of human tumors. The protein may cause inflammation around tumors that, among other things, protects them.
"Tumors are apparently using inflammation to escape the normal surveillance done by immune cells," says study co-leader Dr. Martin Oft.
Discovered 5 years ago, IL-23 controls a number of genes involved in the body's response to infection and other challenges. In many cases, says Dr. Oft, the immune response basically starts with IL-23.
The protein also plays a critical role in causing inflammation associated with autoimmune disorders such as Crohn's disease, multiple sclerosis, and rheumatoid arthritis, where the body essentially attacks itself.
"We know that IL-23 drives the inflammation that causes the tissue damage in autoimmune disorders," says Dr. Robert Kastelein, who co-led the study. "And it does the same thing in tumors."
By promoting inflammation, he says, tumors are able to induce new blood vessels, a process called angiogenesis that is critical to both cancer and fighting infections.
When the immune system mobilizes, one of the first changes in the local area is the formation of new blood vessels and the recruitment of inflammatory cells to help fight the infection. Under normal circumstances, this inflammation is then suppressed and educated immune cells arrive to "mop up" the infection.
But tumors, on the other hand, perpetuate the inflammation around them and never make it to the step when tumor-eliminating immune cells arrive on the scene.
The researchers found that mice born without IL-23 were protected against cancer. The mice were also protected when their IL-23 was blocked by antibodies, suggesting that a similar strategy might one day be possible against human cancers.
In the absence of inflammation caused by IL-23, the researchers conclude, immune cells can do their jobs and kill precancerous cells.
The findings, published online May 10 in Nature, come at a time when many researchers are investigating the relationship between cancer and chronic inflammation and the biological processes they seem to share.
"People have felt for 100 years that there's a link between inflammation and cancer, but I don't think anyone has known exactly what that link was," says Dr. Oft.
"We think this molecule is a key link that brings it all together," he says.
By Edward R. Winstead