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Beta Blockers May Lower Stress, Help Boost Immunotherapy Treatment Response

A study, conducted at Penn State College of Medicine, demonstrated that patients with melanoma who received immunotherapy while also taking a specific type of beta blocker lived longer than those who received immunotherapy alone.
BY Kristie L. Kahl
PUBLISHED January 17, 2018
Commonly known to prevent heart attacks and lower blood pressure, beta blockers may now have a whole other indication: to boost immunotherapy treatments for patients with cancer.

A study, conducted at Penn State College of Medicine, demonstrated that patients with melanoma who received immunotherapy while also taking a specific type of beta blocker lived longer than those who received immunotherapy alone.

Beta blockers are designed to slow a patient’s heart rhythm; however, they may also affect immune cells and improve immune function, according to Todd Schell, Ph.D., professor of microbiology and immunology at Penn State College of Medicine.

“Cancer suppresses many aspects of the immune system,” he said in an interview with CURE. “Lowering stress is known to improve the immune response to infections and cancer. Thus, lowering the stress response by administering beta blockers is expected to work together with immunotherapy to improve the overall immune response to cancer and provide a stronger benefit than either treatment alone.”

In addition, previous studies prompted the researchers to conduct the study.

“We considered that patients with certain cancers, such as breast cancer, have an improved prognosis if they had been prescribed beta adrenergic receptor antagonists (i.e. beta blockers) for a non-cancer condition,” Schell said. “In addition, signaling through beta adrenergic receptors, the receptors that respond to the stress hormones epinephrine and norepinephrine, inhibits the immune system.”

Therefore, the researchers evaluated whether the beta blockers that patients were taking for another condition had any impact on their response to immunotherapy, specifically among patients with metastatic melanoma.

“We chose metastatic melanoma patients for this study since several types of immunotherapy are approved to treat this disease but the majority of patients do not currently experience long-term benefits from immunotherapy,” Schell explained.

Schell and colleagues analyzed data from 195 patients with metastatic melanoma who were treated with immunotherapy between 2000 and 2015, 62 of which were also taking beta blockers. They then compared survival between patients who took beta 1-selective blockers, pan beta blockers and no beta blockers.

Five years after receiving immunotherapy, approximately 70 percent of patients who received pan beta blockers were alive compared with 25 percent of those who took beta 1-selective blockers or no beta blockers at all.

Because beta blockers are currently considered widely available, Schell noted the findings could improve treatment options for patients with cancer. In particular, because the beta blocker they found to be most effective – pan beta blockers – ended up also being the least prescribed amongst its drug class.

“Pan-beta blockers are safe and inexpensive drugs that have been in use for over 40 years to treat angina,” he added. “Since then, use of these drugs has been expanded to treat a number of conditions including high blood pressure, congestive heart failure and anxiety. Our findings support that pan beta-blockers have a potential to be again repurposed to enhance the efficacy of immunotherapeutic drugs used for the treatment of cancer.”

To further support these results, the researchers also performed a parallel experiment in mice with melanoma who were treated with immunotherapy and with or without the pan beta blocker propranolol. Similarly, mice treated with propranolol experienced significantly delayed tumor growth and increased survival when combined with immunotherapy.

Since this study was retrospective, Schell noted that a clinical trial should be conducted to specifically determine the clinical benefit of pan-beta blockers on immunotherapy for metastatic melanoma.

“A clinical trial is planned in combination with a specific type of immunotherapy called anti-PD-1 therapy,” he added. “This therapy currently induces durable complete cancer regressions in about 15 percent of metastatic melanoma patients, so there is the potential to further improve this response rate with the addition of pan-beta blockers. We will pursue studies to better understand how the anti-tumor immune response is improved with this combination therapy.”
 
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