Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice

• Published in: Oncoimmunology Vol. 7; no. 3; p. e1405205
• Main Authors: Kokolus, Kathleen M, Zhang, Ying, Sivik, Jeffrey M, Schmeck, Carla, Zhu, Junjia, Repasky, Elizabeth A, Drabick, Joseph J, Schell, Todd D
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2018; Taylor & Francis Group
• Subjects: beta-adrenergic receptor; beta-blockers; Brief Report; immunotherapy; metastatic melanoma patients; mice; Mice; Beta-adrenergic receptor; Beta-blockers; Metastatic melanoma patients; Immunotherapy
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2017.1405205

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 β 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.