Immunology researchers uncover pathways that direct immune system to turn 'on' or 'off'

by Annie Deck-Miller

(Medical Xpress)—A key discovery explaining how components of the immune system determine whether to activate or to suppress the immune system, made by Kelvin Lee, MD, Professor of Oncology and Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park Cancer Institute (RPCI), and colleagues led to published findings being selected as the "Paper of the Week" by the Journal of Biological Chemistry (JBC). The honor places his work among the top 2 percent—in terms of significance and overall importance—of the year's manuscripts reviewed by the journal.

This research focused on the immune system's (DCs), crucial cells that initiate and regulate immune responses. For example, the dendritic cells activate T lymphocytes to fight an infection or cancer. Curiously, they are also known to suppress the immune response. Determining when DCs turn the immune response "on" or "off" is a major question in immunology.

For this project, Dr. Lee's team explored two receptors (called CD80 and CD86) expressed on the surface of dendritic cells that trigger the cells to make either immune-stimulating factors (interleukin-6) or immune-suppressive factors (indolemine 2, 3 dioxygenase, IDO). They defined the intracellular pathways by which the receptors triggered each response and also uncovered a previously unrecognized interaction with another receptor called Notch-1.

Understanding how these pathways are put together opens the door to targeting components of the pathway so physicians can manipulate the dendritic cells to either activate or suppress the immune system in a way that's therapeutically beneficial.

"Activating the immune response would enhance a patient's response to a vaccine designed to prevent a cancer from growing or recurring," explains Dr. Lee. "Suppressing or blocking an unwanted would be helpful in organ-transplant cases, to prevent rejection, or in autoimmune diseases like lupus and rheumatoid arthritis."

With regard to cancer, Dr. Lee explains how manipulating the CD80/CD86 pathway could impact treatment for , a cancer of a type of white blood cell in the bone marrow.

"Myeloma cells use this pathway to survive and grow by inducing the DC to make IL-6—which promotes the ' survival—and IDO, which blocks anti-cancer responses," he says. "Targeting this pathway would be a novel treatment strategy for multiple myeloma."

The paper was published March 14, 2014, in JBC and is available online at jbc.org.

add to favorites email to friend print save as pdf

Related Stories

Cancer vaccine could use immune system to fight tumors

Feb 27, 2014

Cincinnati Cancer Center (CCC) and UC Cancer Institute researchers have found that a vaccine, targeting tumors that produce a certain protein and receptor responsible for communication between cells and the body's immune ...

Discovery brings cancer immune therapies a step closer

Feb 05, 2014

(Medical Xpress)—The development of new therapies to enhance the body's immune response to cancer is much closer after University of Otago scientists identified a pathway that alters the immune response ...

Recommended for you

Could trophoblasts be the immune cells of pregnancy?

Dec 18, 2014

Trophoblasts, cells that form an outer layer around a fertilized egg and develop into the major part of the placenta, have now been shown to respond to inflammatory danger signals, researchers from Norwegian University of ...

Moms of food-allergic kids need dietician's support

Dec 18, 2014

Discovering your child has a severe food allergy can be a terrible shock. Even more stressful can be determining what foods your child can and cannot eat, and constructing a new diet which might eliminate entire categories ...

Multiple allergic reactions traced to single protein

Dec 17, 2014

Johns Hopkins and University of Alberta researchers have identified a single protein as the root of painful and dangerous allergic reactions to a range of medications and other substances. If a new drug can ...

User comments

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.