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
Review

Abstract

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.

Keywords

Stress Catecholamines Immunosuppression Immunotherapies Nervous system 

Abbreviations

ADCC

Antibody-dependent cell-mediated cytotoxicity

COX

Cyclo-oxygenase

DC

Dendritic cell

EGFR

Epithelial growth factor receptor

EPI

Epinephrine

IDO

Indolamine-2,3-oxygenase

MAPK

Mitogen-activated protein kinase

MDSC

Myeloid-derived suppressor cell

NE

Norepinephrine

NK

Natural killer

PKA

Protein kinase A

rhIL-2

Recombinant human IL-2

SNS

Sympathetic nervous system

TAM

Tumor-associated macrophage

Treg

Regulatory T cell

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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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