The immune system protects the body from invading bacteria and viruses. Often, it also eliminates cancer cells at their earliest stages, before they grow uncontrolled. But some cancer cells can 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 the Department of Cancer Immunotherapeutics and Tumor Immunology, have uncovered one of the tools cancer cells use in their evasive tactics. Writing in the February issue of Cancer Cell, Marcin Kortylewski, Ph.D., Hong Xin, Ph.D., Yu and other members of her laboratory showed that some cancer cells use a single protein to block the immune system in two different ways.
Researchers have long known that the protein called STAT3 — short for signal transducer and activator of transcription 3 — contributes to the development of cancer. It works in many ways, pushing cancer cells to grow out of control, preventing them from self-destructing (as abnormal cells normally would) and driving angiogenesis, the growth of new blood vessels, to feed tumors.
STAT3 also protects cancer cells from the immune system. In the current study, Yu and her team figured out that one of the ways that STAT3 does this is by controlling the production of two separate but related proteins: interleukin 12, or IL-12, and another interleukin, IL-23.
IL-12 normally works to boost the immune system, while IL-23 restrains it. The team showed that STAT3 suppresses IL-12 and promotes IL-23 in the immune cells that get into tumors. In effect, STAT3 stifles the immune system at the same time it protects tumor cells.
In a healthy body, IL-12 and 23 remain in balance, which keeps the immune system alert but under control. In tumors, however, STAT3 goes wild, pushing up levels of IL-23, which suppresses the immune system. At the same time, STAT3 virtually knocks out IL-12 levels, preventing it 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 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.
According to Kortylewski, assistant research scientist and lead author on the paper, researchers have seen pieces of the puzzle for years.
“Others have shown that IL-23 promotes tumor growth and angiogenesis, for example” he said, “but this is the first time anyone has shown that STAT3 is the molecule that controls IL-23 levels in the immune cells within tumors.”
Other City of Hope researchers on the study include Xin, a research fellow and co-lead author for the paper, Maciej Kujawski, Ph.D., senior research fellow, Heehyoung Lee, Ph.D., assistant research scientist, and Yong Liu, Ph.D., research fellow, all from the Department of Cancer Immunotherapeutics and Tumor Immunology.
