Treg Cells Continue Suppressing Immunotherapy Even After They Are Eliminated

Treg cell activity suppresses the immune response and therefore stops the cancer-fighting effect of the immunotherapy treatments; however, eliminating the Treg cells does not end their suppressive qualities, according to new research.

In a study recently published in Nature Immunology, researchers investigated the effects of immune cell activity that may limit immunotherapy’s effectiveness. T cells fight the infection and Treg cells send the signal to the T cells to stop fighting the threat. Immunotherapies super-charge the immune system to fight the cancer, and when the Tregs come in to suppress the immune response, they also stop the cancer-fighting effect.

The researchers found that eliminating the Treg cells does not provide any benefits to patients and does not eliminate their suppressive qualities, because when the Tregs die they become more suppressive rather than negated.

The study found that when the Treg cells die they release small metabolites called ATP, which help supply energy to the body. The dying Tregs quickly convert the ATP to adenosine which then targets the T-cells—this makes the T cells unhealthy and negatively affects how they function, the study found.

“It’s a double-edged sword: If they do not die, they are suppressive. But if they die, they are even more suppressive,” senior study author Weiping Zou, MD, PhD, Charles B. de Nancrede Professor of surgery, immunology, pathology and cancer biology at the University of Michigan, said in a statement. “Nobody expected this — it was a total surprise. But it likely explains why you don’t see benefit when you induce Treg apoptosis."

Although immunotherapy has demonstrated many benefits and revolutionized cancer treatment, there remains to be many limitations and unanswered questions. The researchers are now looking to limit the negative function of Treg cells by forming a roadblock to stop the cells from migrating to the tumor microenvironment in addition to controlling the suppressive activity.