Beta blockers may make checkpoint inhibitors more reliable

A preclinical study suggests that beta blocker medications, commonly prescribed for hypertension and cardiac arrhythmia among other conditions, may be the key to improving the reliability of checkpoint inhibitor medications in the treatment of cancers such as melanoma.

In a paper published online ahead of print in Cancer Research (Aug. 17, 2017), investigators report that the immune regulator molecules known as beta-2 (β2) andrenergic receptors appear to control the functionality of some key immune cells. When exposed to environmental stressors, these molecules cause the cells to produce more of the stress hormone norepinephrine. This protects normal cells from some damaging effects, but can also impair the immune system’s ability to fight cancer, they note.

Further studies showed that the β2 andrenergic receptor ADRB2 could be induced to reduce its signaling through the use of beta-blocker medications. This, in turn, might improve the efficacy of anti-PD-1 checkpoint blockade therapy.

“Our bodies respond to certain types of stress — such as fear and anxiety, heat, cold, pain, depression and even attack by cancer cells — in the same way. We jump into ‘fight or flight’ mode, and the sympathetic nervous system dials up the release of norepinephrine,” senior author Elizabeth Repasky, PhD, said in a press release. Dr. Repasky is the Dr. William Huebsch Professor of Immunology at the Roswell Park Cancer Institute in Buffalo. 

“For reasons that we don’t entirely understand yet, prolonged exposure to these stressors often makes our immune cells much less effective. But we demonstrate here that beta blockers, by reducing adrenergic signaling, allow anti-tumor immune cells to become much stronger, and give immunotherapies, and in particular checkpoint inhibitors, a much better chance to work.”

Dr. Marc Ernstoff, the Katherine Anne Gioia Chair of Medicine at Roswell Park, said in the release that he expects to soon initiate a multicent​re clinical study based on these findings.

“The possibility of improving responses to checkpoint inhibitors and perhaps expanding the numbers of patients who can benefit from them by pairing them with drugs that have been broadly available for years and are generally very well tolerated is quite compelling,” said Dr. Ernstoff. “We look forward to determining whether an approach that combines anti-PD-1 therapy with a beta blocker will be as effective as these intriguing preclinical studies suggest.”​