A new study led by the Dana-Farber Cancer Institute scientists opens new prospects for cancer therapy: by converting a cancer cell’s best friends in the immune system to become its greatest enemy. In the international cooperative study published in the Science, researchers of the Dana-Farber Cancer Institute, Harvard Medical School, Boston Children’s Hospital and Stanford University, have showed us a mechanism that allows the important immune cells to keep the stability and better control of their more militant brothers cells, thereby protecting the normal, healthy tissue from attack.
This new study has great significance for cancer immunotherapy: by using drugs to block this mechanism, it may be possible to turn the attack-suppressing cells into a tumor-attacking cells.
“Our findings put forward a new strategy for immune system-based cancer therapies by targeting a genetic pathway within cells that are usually restrain the immune response to cancer, and we may be able to convert them into cancer fighters. Now the challenge is to develop antibodies and small molecule drugs so that this change can be triggered” said the senior author of the paper, Harvey Cantor, MD, of Dana-Farber and Harvard.
Researchers expect to understand the biology behind a fundamental part of the immune response. When response to the anti-infective or inflammatory, immune system cells known as effector T cells (Teffs) undergo rapid changes – armed themselves and change into groups to target specific types of diseased cells. The second type of immune system cell refers to regulatory T cells (Tregs), which always remain in a stable and unchanging state even when they join battle. Such sustained unchangeable features are critical as Tregs’ role is to control Teffs and prevent them from damaging healthy tissue
Cantor and his colleagues set out to investigate Tregs’ mechanism of maintaining stability. They pointed out that, Tregs typically had high levels of protein Helios, which is a transcription factor that helps switch genes on and off. They then discovered that Tregs with low levels of Helios were quite unstable – due to the instability they are unable to suppress the immune response.
When they studied mice that can not genetically generate Helios, they discovered these T cells and antibodies attack normal tissues of mice. Moreover, animal Tregs also became Teffs, and joined the immune system assault.
Along with the Dana-Farber Cancer Institute and the Boston Children’s Hospital, Haining Nicholas, the researchers found that Helio had a stable effect on the upregulating – increasing activity of a series of genes known as the STAT5 pathway.
After completing the study, Cantor and his colleagues have begun to investigate whether their findings can be used for cancer treatment. “The next step is to identify antibodies and small molecules drugs that can target the Helios or gens in Helios signaling pathway,” said Kim Hye-Jung, the lead author of the study. “We are currently testing a variety of drugs.”
Stable inhibitory activity of regulatory T cells requires the transcription factor Helios, Science.