Cancer Immunology, Immunotherapy

, Volume 63, Issue 11, pp 1115–1128 | Cite as

A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response

  • Jason W.-L. Eng
  • Kathleen M. Kokolus
  • Chelsey B. Reed
  • Bonnie L. Hylander
  • Wen W. Ma
  • Elizabeth A. Repasky


Long conserved mechanisms maintain homeostasis in living creatures in response to a variety of stresses. However, continuous exposure to stress can result in unabated production of stress hormones, especially catecholamines, which can have detrimental health effects. While the long-term effects of chronic stress have well-known physiological consequences, recent discoveries have revealed that stress may affect therapeutic efficacy in cancer. Growing epidemiological evidence reveals strong correlations between progression-free and long-term survival and β-blocker usage in cancer patients. In this review, we summarize the current understanding of how the catecholamines, epinephrine and norepinephrine, affect cancer cell survival and tumor progression. We also highlight new data exploring the potential contributions of stress to immunosuppression in the tumor microenvironment and the implications of these findings for the efficacy of immunotherapies.


Stress Catecholamines Immunosuppression Immunotherapies Nervous system 



Antibody-dependent cell-mediated cytotoxicity




Dendritic cell


Epithelial growth factor receptor






Mitogen-activated protein kinase


Myeloid-derived suppressor cell




Natural killer


Protein kinase A


Recombinant human IL-2


Sympathetic nervous system


Tumor-associated macrophage


Regulatory T cell



We thank Jeanne Prendergast for editorial assistance. This work was supported by National Institute of Health Grants R01 CA135368 and T32 CA 085183 and Breast Cancer Research and Education Fund through NY State Department of Health contract # C028252.

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jason W.-L. Eng
    • 1
  • Kathleen M. Kokolus
    • 1
  • Chelsey B. Reed
    • 1
  • Bonnie L. Hylander
    • 1
  • Wen W. Ma
    • 2
  • Elizabeth A. Repasky
    • 1
  1. 1.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of MedicineRoswell Park Cancer InstituteBuffaloUSA

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