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

Kathleen M. Kokolus, Ying Zhang, Jeffrey M. Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A. Repasky, Joseph Drabick, Todd Schell

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 β 2 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.

Original languageEnglish (US)
Article numbere1405205
JournalOncoImmunology
Volume7
Issue number3
DOIs
StatePublished - Mar 4 2018

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Immunotherapy
Melanoma
Adrenergic Receptors
Survival
Interleukin-2
Neoplasms
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

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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 β 2 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.",
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Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice. / Kokolus, Kathleen M.; Zhang, Ying; Sivik, Jeffrey M.; Schmeck, Carla; Zhu, Junjia; Repasky, Elizabeth A.; Drabick, Joseph; Schell, Todd.

In: OncoImmunology, Vol. 7, No. 3, e1405205, 04.03.2018.

Research output: Contribution to journalArticle

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AU - Kokolus, Kathleen M.

AU - Zhang, Ying

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AU - Zhu, Junjia

AU - Repasky, Elizabeth A.

AU - Drabick, Joseph

AU - Schell, Todd

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