Team finds molecule that could improve cancer vaccines and therapy for other diseases

Nov 22, 2007

Investigators at St. Jude Children's Research Hospital have discovered a new signaling molecule that prevents immune responses from running amok and damaging the body. The finding could lead to the development of new treatments for cancer, using vaccines; for autoimmune diseases, such as Type 1 diabetes; and for inflammatory diseases, such as inflammatory bowel disease (IBD) and asthma.

The St. Jude team discovered that specialized immune lymphocytes called regulatory T cells release a protein complex composed of two proteins called Ebi3 and Il12a. This protein complex acts like a brake on the activity of the aggressive immune cells called effector T lymphocytes. A report on this discovery appears in the journal Nature Nov. 22, 2007.

The newly recognized protein complex is one of a large group of signaling molecules called cytokines that cells use to communicate with each other. Since the immune system cytokines are called interleukins, the St. Jude team named this protein interleukin-35 (IL-35). Most cytokines stimulate immune system cells by driving the immune attack or causing inflammation. However, IL-35 is one of the few signaling molecules known to inhibit immune system activity.

“The discovery of IL-35 is important because the manipulation of regulatory T cells is a key goal of immunotherapy,” said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology, and the paper’s senior author. Immunotherapy is the treatment of infections, cancer or other diseases by manipulating the immune system to enhance or restrict its activity. Despite the fact that regulatory T cell-mediated immunotherapy holds promise for patients, the molecules responsible for the cells’ ability to suppress immune system activity are largely unknown, a problem that has slowed progress in this field.

The St. Jude team showed that the genes that produce IL-35 (Ebi3 and II12a) are active in regulatory T cells but not in effector T cells and are critical to regulatory T cell function. In fact, regulatory T cells that lack the Ebi3 and II12a genes lose much of their ability to suppress effector T cells. In addition, these regulatory T cells are unable to cure mouse models of an inflammatory disease that closely resembles human IBD.

When the researchers added regulatory T cells to a culture dish with effector T cells, the regulatory T cells dramatically increased their production of the decoded forms (messenger RNA) of the Ebi3 and II12a genes. This suggests that effector T cells had released signals that stimulated the regulatory T cells to decode these genes and make IL-35, the researchers reported.

“The identification of IL-35 as a key cytokine released by regulatory T cells adds significantly to our understanding of how these cells prevent immune responses from running out of control and causing damage,” Vignali said. “Regulatory T cells are seen as a major impediment to the development of effective anti-cancer vaccines and may prevent sterilizing immunity in certain chronic infections, such as hepatitis C and tuberculosis. As the maximal suppressive function of regulatory T cell is dependent on IL-35, blocking its activity may reduce regulatory T cell function and reduce their ability to block anti-tumor immune responses. Thus, treatments that block IL-35 activity may make anti-cancer vaccines more effective.” Vaccines work by stimulating the immune system to recognize and attack specific targets, such as germs or cancer cells.

“Autoimmune diseases and inflammatory diseases are caused by a breakdown of the normal regulatory processes that control our immune system,” Vignali said. “Novel treatments that add IL-35 or boost IL-35 activity may also provide new therapeutic opportunities for these diseases.”

“The identification of IL-35 is especially exciting because, to date, it is the only known cytokine that is made specifically by regulatory T lymphocytes and can suppress the activity of effector T cells directly,” said Lauren Collison, Ph.D., a postdoctoral fellow in Vignali’s laboratory who contributed significantly to the project. “This suggests that controlling levels of IL-35 in patients might one day allow clinicians to dial the immune response up or down depending on the needs of the patient.” Collison is the paper’s first author.

Source: St. Jude Children's Research Hospital

Explore further: 3-D printing offers innovative method to deliver medication

add to favorites email to friend print save as pdf

Related Stories

A first of its kind tool to study the histone code

Feb 10, 2015

University of North Carolina scientists have created a new research tool, based on the fruit fly, to help crack the histone code. This research tool can be used to better understand the function of histone proteins, which ...

Helping horses come to term

Aug 02, 2013

It is not only humans that sometimes experience difficulty having children. Horses too have a low birth rate, with many pregnancies failing within the first few weeks after conception. The reason is currently ...

A secret to making macrophages (w/ Video)

Jul 18, 2013

Biologists at the California Institute of Technology (Caltech) have worked out the details of a mechanism that leads undifferentiated blood stem cells to become macrophages—immune cells that attack bacteria ...

Scientists map mouse genome's 'mission control centers'

Nov 19, 2014

When the mouse and human genomes were catalogued more than 10 years ago, an international team of researchers set out to understand and compare the "mission control centers" found throughout the large stretches ...

Recommended for you

3-D printing offers innovative method to deliver medication

4 hours ago

3-D printing could become a powerful tool in customizing interventional radiology treatments to individual patient needs, with clinicians having the ability to construct devices to a specific size and shape. That's according ...

Mystery of the reverse-wired eyeball solved

Feb 27, 2015

From a practical standpoint, the wiring of the human eye - a product of our evolutionary baggage - doesn't make a lot of sense. In vertebrates, photoreceptors are located behind the neurons in the back of the eye - resulting ...

Neurons controlling appetite made from skin cells

Feb 27, 2015

Researchers have for the first time successfully converted adult human skin cells into neurons of the type that regulate appetite, providing a patient-specific model for studying the neurophysiology of weight ...

Quality control for adult stem cell treatment

Feb 27, 2015

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.