Why Slowing the Stress Response Might Improve Immunotherapy
The goal of immunotherapy is to turn on the immune response to fight cancer. Unfortunately, many things weaken the immune response, including stress. A new clinical trial open at Roswell Park is investigating whether beta blockers, which calm the body’s response to stress, can boost immunotherapy in patients with advanced melanoma.
Beta blockers have been around for decades and are commonly used to treat stress-related conditions like hypertension (high blood pressure), abnormal heart conditions, migraines and anxiety. They work by blocking the effects of adrenaline, a hormone produced by the stress response — otherwise known as “fight or flight.”
Stress and the immune system
When faced with stress, your body releases hormones that cause the heart to beat faster, blood pressure to rise and muscles to tighten. This is useful in dangerous situations, as it makes us more alert and ready to face (or run away from) danger, but it also suppresses the immune cells that our body needs to fight disease, including cancer.
The immune system is constantly surveilling the body for signs of infection and disease. When a threat is identified, specialized immune “soldiers” called T cells are quickly released to attack harmful bacteria, viruses or cancer cells. The immune response also causes inflammation, which is not healthy in the long run.
The body has developed ways to speed up and slow down the immune response to balance the need to fight the dueling threats of disease and inflammation. Similar to a vehicle, T cells have accelerators and brakes that speed up or slow down their attacks. If the immune response is stopped before a threat like cancer is eliminated, then tumors can grow and spread.
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Beta blockers and immunotherapy
Pembrolizumab (Keytruda) is an immunotherapy drug that takes the brakes off T cells, allowing the immune system to recognize and attack cancer. The FDA approved this drug in 2014 to treat melanoma, and it can be very effective in shrinking and eliminating tumors. We now have evidence that beta blockers can help immunotherapy drugs like pembrolizumab work better. Elizabeth Repasky, PhD, Professor of Oncology in the Department of Immunology, recently discovered that the immune response to cancer is weakened by cold temperatures. Cold is a stressor, and prolonged exposure triggers the fight-or-flight response. Beta blockers calm the stress response, which might make immunotherapy drugs more effective.
A new trial is currently being conducted here at Roswell Park to see whether the beta blocker propranolol hydrochloride, when given together with pembrolizumab, can improve responses to immunotherapy in patients with advanced (stage IIIC-IV) melanoma that cannot be removed by surgery. We know that this beta blocker is safe, and we are hopeful that this combination will help our patients.
The study is funded by the Roswell Park Alliance Foundation and two generous donors. For more information, please visit our clinical trials page, call 1-800-ROSWELL (1-800-767-9355), or e-mail firstname.lastname@example.org (trial 3618).