The immune system protects the body from invading bacteria and viruses, but it also holds another duty. It protects against cancer, often destroying tumor cells early in their lives, well before they start doing harm.
Problems arise when cancer cells manage to escape the body’s defenses, take hold and grow out of control.
 Marcin Kortylewski probes the role of STAT3 in the development and growth of tumor cells. (Photo by Walter Urie) |
Now, researchers led by Hua Yu, Ph.D., professor in City of Hope’s Department of Cancer Immunotherapeutics and Tumor Immunology, have uncovered one of the tools cancer cells use to avoid the immune system’s vigilance.
Yu, along with Marcin Kortylewski, Ph.D., assistant research scientist, Hong Xin, Ph.D., research fellow, and other members of Yu’s lab, showed that some cancer cells use a single protein to block the immune system — in two different ways.
Researchers have long known that a protein called STAT3 (shorthand for signal transducer and activator of transcription 3) can be a tumor’s best friend. STAT3 helps tumor cells in many ways: egging them on to grow out of control; blocking them from self-destructing, as abnormal cells normally would; and helping to feed them by driving the growth of new blood vessels within tumors.
STAT3 also acts as a sort of bodyguard, protecting cancer cells from the immune system. Yu and her team figured out that one of the ways STAT3 shields tumors from the immune system is by controlling the production of two separate but related proteins, called interleukins.
In normal conditions, interleukin 12, or IL-12, revs up the immune system to fight disease. Its cohort, IL-23, normally holds back the immune system when all is well.
In a healthy body, IL-12 and 23 remain in balance, and this keeps the immune system alert but under control. But in tumors, STAT3 goes wild. It pushes up levels of IL-23, which suppresses the immune system, and at the same time virtually knocks out IL-12 levels, keeping that protein from activating the immune system.
The result is a double-barreled action that shuts down the immune system in the area around the tumor, allowing cancer cells to grow freely.
The study builds on earlier findings from Yu and her team showing that STAT3 could protect cancer cells from the immune system. “We’ve known this for years, but we have just made a new link,” Yu said.
Yu and her team ultimately hope to build on their work to find drugs that can stop STAT3 from helping tumors develop and grow.
