Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Hanson, Erik D.; Bates, Lauren C.; Moertl, Kaileigh; Evans, Elizabeth S.

doi:10.3390/endocrines2020012

Cited by 3 publications

(3 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, while some studies showed an inhibitory effect of epinephrine on NK cells 25,26,70 , other in vivo studies demonstrated an increase in NK cell cytotoxicity 31,33,52 . In line with an increased cytotoxicity, our metabolic analysis discovered a prolonged CD16-induced glycolytic activity after β2AR stimulation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic stimulation desensitizes β2 adrenergic receptor responses in Natural Killer cells

Watzl,

Jürgens,

Claus

et al. 2024

Preprint

View full text Add to dashboard Cite

Psychosocial stress affects the function of the immune system via activation of the sympathetic nervous system and the release of the neurotransmitter epinephrine. Acute and chronic stress can have opposing effects on the immune system and chronic stress is correlated with higher incidences of infections and cancer. Here, we study the effect of epinephrine on the function of human Natural Killer (NK) cells as important innate lymphocytes for immune reactions against infections and cancer. Epinephrine-mediated stimulation of the β2 adrenergic receptor (β2AR) on NK cells inhibited early signaling events and blocked the function of the integrin LFA-1. This led to a reduced adhesion of NK cells to ICAM-1, explaining how NK cells are mobilized into the peripheral blood upon acute stress. Additionally, epinephrine stimulation transiently reduced NK cell degranulation, serial killing, cytokine production, and affected metabolic changes upon NK cell activation via the cAMP-PKA pathway. Repeated exposure to β2AR agonists resulted in the desensitization of the β2AR via a PKA feedback loop-initiated G-protein switch. Therefore, acute epinephrine stimulation of chronically β2AR stimulated NK cells no longer resulted in inhibited signaling and reduced LFA-1 activity, recapitulating the opposing effects of acute versus chronic stress. Sustained stimulation by long-acting β2 agonists (LABA) not only inhibited NK cell functions but also resulted in desensitization of the β2AR. However, peripheral NK cells from LABA-treated asthma patients still reacted unchanged to epinephrine stimulation, demonstrating that local LABA administration does not result in detectable systemic effects on NK cells.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In vivo, epinephrine release during acute stress, exercise or medication can quickly and transiently increase NK cell numbers in peripheral blood [51][52][53] . This may be linked to changes in NK cell adhesion to endothelial cells 54 which is mediated by the integrin LFA-1.…”

Section: β2 Agonists Block Lfa-1 Activity and Cytotoxicity Of Nk Cellsmentioning

confidence: 99%

Chronic stimulation desensitizes β2 adrenergic receptor responses in Natural Killer cells

Watzl,

Jürgens,

Claus

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…As we previously reported that men with prostate cancer have attenuated epinephrine responses to acute exercise ( 34 ), it interesting that neither T cells (current study) or NK cell mobilization ( 21 ) were adversely impacted. This suggests that other factors may compensate for the reduced epinephrine response, such as changes in shear stress or myokine release ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Hanson

Sakkal

Bates

et al. 2023

Front. Sports Act. Living

Self Cite

View full text Add to dashboard Cite

BackgroundReduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls.MethodsAge-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise.ResultsAt 0 h, conventional T cell counts increased by 45%–64% with no differences between groups. T cell frequency decreased by −3.5% for CD3+ and −4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of −4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was −18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h.ConclusionFollowing acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

show abstract

Chronic stimulation desensitizes β2‐adrenergic receptor responses in natural killer cells

Jürgens,

Claus,

Wingert

et al. 2024

Eur J Immunol

View full text Add to dashboard Cite

Adrenergic receptors (ARs) are preferentially expressed by innate lymphocytes such as natural killer (NK) cells. Here, we study the effect of epinephrine‐mediated stimulation of the β2‐adrenergic receptor (β2AR) on the function of human NK cells. Epinephrine stimulation inhibited early NK cell signaling events and blocked the function of the integrin LFA‐1. This reduced the adhesion of NK cells to ICAM‐1, explaining how NK cells are mobilized into the peripheral blood upon epinephrine release during acute stress or exercise. Additionally, epinephrine stimulation transiently reduced NK cell degranulation, serial killing, and cytokine production and affected metabolic changes upon NK cell activation via the cAMP‐protein kinase A (PKA) pathway. Repeated exposure to β2AR agonists resulted in the desensitization of the β2AR via a PKA feedback loop‐initiated G‐protein switch. Therefore, acute epinephrine stimulation of chronically β2AR stimulated NK cells no longer resulted in inhibited signaling and reduced LFA‐1 activity. Sustained stimulation by long‐acting β2‐agonists (LABA) not only inhibited NK cell functions but also resulted in desensitization of the β2AR. However, peripheral NK cells from LABA‐treated asthma patients still reacted unchanged to epinephrine stimulation, demonstrating that local LABA administration does not result in detectable systemic effects on NK cells.

show abstract

Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Cited by 3 publications

References 92 publications

Chronic stimulation desensitizes β2 adrenergic receptor responses in Natural Killer cells

Chronic stimulation desensitizes β2 adrenergic receptor responses in Natural Killer cells

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Chronic stimulation desensitizes β2‐adrenergic receptor responses in natural killer cells

Contact Info

Product

Resources

About