Adrenergic stress constrains the development of anti-tumor immunity and abscopal responses following local radiation

Minhui Chen, Guanxi Qiao, Bonnie L. Hylander, Hemn Mohammadpour, Xiang-Yang Wang, John R. Subjeck, Anurag K. Singh and Elizabeth A. Repasky ()
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Minhui Chen: Roswell Park Comprehensive Cancer Center
Guanxi Qiao: Roswell Park Comprehensive Cancer Center
Bonnie L. Hylander: Roswell Park Comprehensive Cancer Center
Hemn Mohammadpour: Roswell Park Comprehensive Cancer Center
Xiang-Yang Wang: Virginia Commonwealth University
John R. Subjeck: Roswell Park Comprehensive Cancer Center
Anurag K. Singh: Roswell Park Comprehensive Cancer Center
Elizabeth A. Repasky: Roswell Park Comprehensive Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The abscopal effect following ionizing radiation therapy (RT) is considered to be a rare event. This effect does occur more frequently when combined with other therapies, including immunotherapy. Here we demonstrate that the frequency of abscopal events following RT alone is highly dependent upon the degree of adrenergic stress in the tumor-bearing host. Using a combination of physiologic, pharmacologic and genetic strategies, we observe improvements in the control of both irradiated and non-irradiated distant tumors, including metastatic tumors, when adrenergic stress or signaling through β-adrenergic receptor is reduced. Further, we observe cellular and molecular evidence of improved, antigen-specific, anti-tumor immune responses which also depend upon T cell egress from draining lymph nodes. These data suggest that blockade of β2 adrenergic stress signaling could be a useful, safe, and feasible strategy to improve efficacy in cancer patients undergoing radiation therapy.

Date: 2020
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DOI: 10.1038/s41467-020-15676-0

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