Reprogramming immune cells to fight tumors from within

Memphis, Tennessee, October 19, 2018

Douglas Green, PhD, in the lab

Doug Green, PhD

Ever let dishes pile up while you deal with a crisis? Scientists at St. Jude Children’s Research Hospital have a new strategy to reprogram certain immune cells inside tumors so that they focus on killing cancer cells rather than tidying up after tumor cells die.

The plan involves a process the scavenger immune cells use to digest the dead and dying tumor cells they pick up for disposal. Researchers showed that disabling the process in the immune cells transformed them from housecleaners to cancer fighters.

Doug Green, PhD, St. Jude Department of Immunology chair, and his colleagues. discovered the process, known as LAP, in 2007. He also led this research. (LAP is short for LC3-associated phagocytosis.)

“Lung and other tumors grew more slowly when LAP was disabled in scavenger immune cells called macrophages in mice,” Green said.  “The search for compounds that would allow us to regulate the process has begun.”

The research appeared in the journal Cell.

Reprogramming macrophages to fight cancer (graphic)

Scientists have a new strategy to enhance the anti-cancer immune response and slow tumor growth. The goal is to reprogram macrophages to eliminate tumor cells. The strategy: Harness a process called LC3-associated phagocytosis (LAP) that’s already at work in macrophages. Discovered in 2007 by Doug Green, Ph.D., chair of the St. Jude Department of Immunology, and his colleagues, LAP helps macrophages digest dead or dying cells, including tumor cells. Now Green and his team have reported that LAP works in macrophages in and around tumors to inhibit inflammation and suppress the anti-tumor response. Disabling LAP changed gene expression in such macrophages. The result? T cells were activated, igniting the anti-tumor response. Research has begun to find drugs to regulate LAP in macrophages.
 

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