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PubMed Publications| Keyword search (4,163 papers available) |  |
"Emamnia N" Authored Publications:
| Title | Authors | PubMed ID | |
|---|---|---|---|
| 1 | Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a β2-adrenergic receptor-dependent manner | Hajiaghayi M; Gholizadeh F; Rahbari N; Emamnia N; Shih SCC; Darlington PJ; | 41906691 SOH |
| Title: | Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a β2-adrenergic receptor-dependent manner | ||||
| Authors: | Hajiaghayi M, Gholizadeh F, Rahbari N, Emamnia N, Shih SCC, Darlington PJ | ||||
| Link: | https://pubmed.ncbi.nlm.nih.gov/41906691/ | ||||
| DOI: | 10.1093/cei/uxag018 | ||||
| Publication: | Clinical and experimental immunology | ||||
| Keywords: | T cell exhaustion; cytotoxic T cells; nebivolol; tumor microenvironment; β; ₂; -adrenergic receptors; | ||||
| PMID: | 41906691 | Category: | Date Added: | 2026-03-30 | |
| Dept Affiliation: |
SOH
1 Department of Biology, School of Health, Concordia University, Montréal, Québec, Canada. 2 Department of Chemical and Materials Engineering, Center for Applied Synthetic Biology, Concordia University, Montréal, Québec, Canada. 3 Department of Electrical and Computer Engineering, School of Health, Concordia University, Montréal, Québec, Canada. 4 Department of Health Kinesiology & Applied Physiology, School of Health, Concordia University, Montréal, Québec, Canada. |
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Description: |
Introduction: Cancers often drive T cells toward an exhausted state characterized by impaired cytotoxicity and upregulation of inhibitory receptors (PD-1, TIM-3, CD38) and transcriptional regulators (TOX, NFATc1). Repeated stimulation in vitro is used to model this process, reflecting chronic antigen exposure in the tumor microenvironment. Stress-derived catecholamines further drive dysfunction through ß-adrenergic receptor (ß-AR) signaling. Here, we examined the impact of nebivolol, an atypical ß1-AR blocker with ß2-biased agonist activity, on T-cell exhaustion and cytotoxicity against breast cancer cells. Methods: Human CD3+ T cells from healthy participants were activated once (early activation) or four times (repeated activation) using CD3/CD28/CD2 T cell activator. Cells were treated in vitro with nebivolol, terbutaline (ß2-agonist), isoproterenol (ß1/ß2-agonist), and metoprolol (ß1-blocker). Exhaustion markers, including PD-1, TIM-3, CD38, and TOX, were measured by flow cytometry and RT-qPCR; NFATc1 by western blot; TNF and IFN-? by ELISA, and cytotoxicity against MCF-7 breast carcinoma cells by co-culture assays. Disruption of the ß2-AR gene (ADRB2) was achieved using CRISPR/Cas9. Results: Nebivolol reduced the proportion of TIM-3+CD38+PD-1+ T cells, downregulated TOX and nuclear NFATc1, and restored ADRB2 expression under repeated activation conditions. Nebivolol enhanced TNF secretion and improved cytotoxicity against MCF-7 cells. In contrast, terbutaline and isoproterenol had no significant effect on exhaustion markers or cytotoxicity. Metoprolol did not inhibit nebivolol's activity, indicating that its effects are not ß1-AR-dependent. Disruption of ADRB2 indicated that nebivolol's anti-exhaustion effects are mediated by ß2-AR. Discussion: These findings show that nebivolol reinvigorates CD4+ and CD8+ T cells following repeated activation, restoring their cytotoxic function against breast cancer cells in vitro. The immunomodulatory activity of Nebivolol is independent of ß1-AR and mediated through ß2-AR, suggesting that biased ß2-AR signaling may represent a potential strategy for modulating T cell exhaustion in the tumor microenvironment. |
