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BUFFALO, NY — 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, the Jacobs Family Chair in Immunology, Professor of Oncology and Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park Comprehensive Cancer Center (Roswell Park), 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 dendritic cells (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.
With regard to cancer, Dr. Lee explains how manipulating the CD80/CD86 pathway could impact treatment for multiple myeloma, a cancer of a type of white blood cell in the bone marrow.
This work has been supported in part by three National Institutes of Health (NIH) grants: awards R01CA140622, R01CA121044 and T32CA085183, from the National Cancer Institute (NCI), and R01AI100157, from the National Institute of Allergy and Infectious Diseases (NIAID). Additional funds were provided by the Multiple Myeloma Research Foundation (MMRF).
The paper was published March 14, 2014, in JBC and is available online at jbc.org.
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In that passage, there are 130 occurrences of the letter "o."
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