Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice. (4th March 2018)

• Record Type: Journal Article
• Authors: Kokolus, Kathleen M.; Zhang, Ying; Sivik, Jeffrey M.; Schmeck, Carla; Zhu, Junjia; Repasky, Elizabeth A.; Drabick, Joseph J.; Schell, Todd. D.
• Is Part Of: Oncoimmunology. Volume 7:Number 3(2018)
• Publication Date: 2018-03-04
• Subjects: Beta-adrenergic receptor -- Beta-blockers -- Immunotherapy -- Metastatic melanoma patients -- Mice; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1405205
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers. This retrospective analysis is reinforced by results showing that βAR blockade enhances the control of murine melanoma growth by anti-(α)PD-1 checkpoint blockade. However, this effect was most significant when β-blocker was combined with dual αPD-1 + high dose interleukin-2 therapy and was reproduced by selective blockade of β2 ARs. These results identify a novel strategy that can be quickly introduced to potentially increase the number of patients who benefit from immune-based therapies.