In a recent study published in the journal Immunity, a team of researchers from St. Jude Children’s Research Hospital characterized a family of immune cells that are used by tumors in order to maintain their malignant status and evade the immune system.
The cells, called myeloid-derived suppressor cells (MDSC) were already known to exist in higher numbers in patients who suffered from several types of cancers. These cells suppress the effector function of T cells, enhancing tumor growth and working against their own hosts.
However, attempts to identify clear cellular markers that can specifically categorize this particular population of cells have not been successful.
The research team used mouse models of cancer to demonstrate that the immunosuppressive effects linked to MDSCs are tightly linked to the function of monocytes, which are responsible for the development of macrophages.
“We have identified the monocytic cells as the important cell to target, not only in cancer but possibly for treatment of autoimmune disorders like rheumatoid arthritis or inflammatory bowel diseases where dampening the immune response could provide relief,” study author Peter Murray, Ph.D., a member of the St. Jude departments of Infectious Diseases and Immunology, said in a news release. “We also identified growth factors and other molecules essential to the survival and function of these monocytic cells. Targeting these molecules could lead to more precise approaches for controlling the immune response at the tumor site.This study marks a significant step in efforts to understand, develop and optimize immunotherapies for treatment of cancer.”
In collaboration with two other laboratories from the same institute, the research team was able to switch off two proteins, MCL1 and FLIP, which led to the loss of granulocytes or monocytes in their animal models. They then observed how this loss affected T cells, showing that the main cells responsible for T cell inhibition are monocytic cells.
“We’ve known for decades that cancer has harnessed the immune system to keep pumping out large numbers of mature and immature myeloid cells from the bone marrow,” Dr. Murray added. “Collaborating with the Opferman and Green laboratories gave us the tools we need to discriminate between the cell populations and identify monocytic cells as the important cells to target with immunotherapies.”