Immune Cell Commander

Date: November 11, 2010

Immunity, June 19, 2009

In the world of cancer immunity, there are commanders and soldiers. Researchers led by Jonathan Powell, M.D., Ph.D., believe they have identified a commander.  They say an enzyme known as mTOR plays a crucial role in directing immune soldier cells known as T-cells toward disease-causing offenders, making it a potential therapeutic target to promote immunity in diseases, including cancer.

T cells come in several varieties and respond to a broad array of environmental signals. When activated, they decide which type of cell to change into to best do a necessary job. For example, Th1 cells help fight cancer or viruses, Th2 cells help fight parasites but also promote allergy and asthma, and Th17 cells help fight bacterial infections.

“Our work suggests that mTOR signaling regulates the decision toward which type of cell that T cells become,” Powell says. “Without mTOR, T cells default to become regulatory cells, so signals leading to the activation of mTOR are required to redirect the cells toward active immunity.”

The research already has led to the development of a novel bone marrow transplant approach to curing sickle cell disease and has spurred the development of three cancer clinical trials. Clinician scientist David Loeb, M.D., is investigating whether blocking mTOR signaling can hinder cancer-originating stem cells in sarcoma patients while Douglas Gladstone, M.D.,  and William Matsui, M.D., are looking at mTOR inhibitors as a treatment for mantle cell lymphoma. Ivan Borello, M.D., plans to use a mTOR inhibitor in an attempt to preserve bone in multiple myeloma patients.

The work was supported by the National Cancer Institute and the National Institute for Allergy and Infectious Diseases.