title: A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response.
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.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors.forename: Jason W-L
authors.initials: JW
authors.lastname: Eng
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Kokolus
authors.forename: Chelsey B
authors.initials: CB
authors.lastname: Reed
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Hylander
authors.forename: Wen W
authors.initials: WW
authors.lastname: Ma
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Repasky
mesh_terms: D000818:Animals; D001007:Anxiety / Q000150:complications; D018450:Disease Progression; D018572:Disease-Free Survival; D004837:Epinephrine / Q000378:metabolism; D005239:Fear; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D009369:Neoplasms / Q000473:pathology* / Q000523:psychology*; D009638:Norepinephrine / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism; D013315:Stress, Psychological; D013564:Sympathetic Nervous System; D059016:Tumor Microenvironment
chemical_list: D007166:Immunosuppressive Agents; D011941:Receptors, Adrenergic; D009638:Norepinephrine; D004837:Epinephrine