Authors: Kathleen M. Kokolus, Ying Zhang, Jeffrey M. Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A. Repasky, Joseph J. Drabick, Todd. D. Schell
Summary:
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 β2ARs. These results identify a novel strategy that can be quickly introduced to potentially increase the number of patients who benefit from immune-based therapies.
Source:
OncoImmunology; 2017, e1405205