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

Author

Listed:
  • 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
    Roswell Park Comprehensive Cancer Center)

  • Elizabeth A. Repasky

    (Roswell Park Comprehensive Cancer Center)

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.

Suggested Citation

  • Minhui Chen & Guanxi Qiao & Bonnie L. Hylander & Hemn Mohammadpour & Xiang-Yang Wang & John R. Subjeck & Anurag K. Singh & Elizabeth A. Repasky, 2020. "Adrenergic stress constrains the development of anti-tumor immunity and abscopal responses following local radiation," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15676-0
    DOI: 10.1038/s41467-020-15676-0
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    Cited by:

    1. Xinyu Tang & Xinrui Mao & Peiwen Ling & Muxin Yu & Hua Pan & Jiaming Wang & Mingduo Liu & Hong Pan & Wen Qiu & Nan Che & Kai Zhang & Feifan Bao & Hongwei Peng & Qiang Ding & Shui Wang & Wenbin Zhou, 2024. "Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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