Reducing the effects of stress on T cells improves immune effectiveness in fighting cancer
Stress hormones deplete immune cells in humans and mice, but beta-blockers help restore them.Researchers at the Salk Institute for Biological Studies have discovered a link between the body's sympathetic response to stress and the depletion of T-killers - lymphocytes that destroy damaged cells in the body. The use of beta-blockers inhibits this link and increases the immune system's effectiveness in fighting tumor cells.
The sympathetic nervous system is responsible for the body's response to stress - the "hit or run" response. Researchers studied the effect on the immune system activity of sympathetic nerves, which in stressful situations produce the messenger hormone norepinephrine. The scientists used cancer and chronic disease models in mice and on human tissue samples to study when and how sympathetic nerves influence T-killers.
The analysis showed that sympathetic nerves produce norepinephrine, which binds to T killer cells using the ADRB1 receptor. T killer cells become depleted over time, losing activity and no longer affecting the disease focus. Such depleted cells express more ADRB1 receptors than their functional counterparts.
To test whether T-killer depletion could be prevented, the researchers tested two approaches to hijacking the interaction between norepinephrine and ADRB1: either removing the receptors altogether or disrupting their function with beta-blockers. Exposure to the drugs, which are used to lower blood pressure, led to more functional T-killers that were better at destroying tumor cells.
Since beta-blockers are already in clinical use and have passed safety trials, the researchers plan to soon begin testing the drugs to improve the effectiveness of therapy in lung cancer patients.