{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:01:13Z","timestamp":1776423673073,"version":"3.51.2"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":88,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2019-06980"],"award-info":[{"award-number":["RGPIN-2019-06980"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003151","name":"Fonds de recherche du Qu\u00e9bec-Nature et technologies","doi-asserted-by":"publisher","award":["2023-2024-B2X-334802"],"award-info":[{"award-number":["2023-2024-B2X-334802"]}],"id":[{"id":"10.13039\/501100003151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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 \u03b2-adrenergic receptor (\u03b2-AR) signaling. Here, we examined the impact of nebivolol, an atypical \u03b21-AR blocker with \u03b22-biased agonist activity, on T-cell exhaustion and cytotoxicity against breast cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 (\u03b22-agonist), isoproterenol (\u03b21\/\u03b22-agonist), and metoprolol (\u03b21-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-\u03b3 by ELISA, and cytotoxicity against MCF-7 breast carcinoma cells by co-culture assays. Disruption of the \u03b22-AR gene (ADRB2) was achieved using CRISPR\/Cas9.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2019s activity, indicating that its effects are not \u03b21-AR-dependent. Disruption of ADRB2 indicated that nebivolol's anti-exhaustion effects are mediated by \u03b22-AR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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 \u03b21-AR and mediated through \u03b22-AR, suggesting that biased \u03b22-AR signaling may represent a potential strategy for modulating T cell exhaustion in the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cei\/uxag018","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:46:51Z","timestamp":1774615611000},"source":"Crossref","is-referenced-by-count":0,"title":["Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a \u03b22-adrenergic receptor-dependent manner"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-7009","authenticated-orcid":false,"given":"Mehri","family":"Hajiaghayi","sequence":"first","affiliation":[{"name":"Department of Biology, School of Health, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Gholizadeh","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Health, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niloufar","family":"Rahbari","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, Center for Applied Synthetic Biology, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Negaralsadat","family":"Emamnia","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Health, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve C C","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, School of Health, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J","family":"Darlington","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Health, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]},{"name":"Department of Health Kinesiology & Applied Physiology, School of Health, Concordia University , Montr\u00e9al, Qu\u00e9bec ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"2026041706064877200_uxag018-B1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"2026041706064877200_uxag018-B2","first-page":"4165","article-title":"The prognostic significance of the tumor-infiltrating programmed cell death-1+ to CD8+ lymphocyte ratio in patients with colorectal cancer","volume":"37","author":"Shibutani","year":"2017","journal-title":"Anticancer Res"},{"key":"2026041706064877200_uxag018-B3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/SLA.0000000000002985","article-title":"Prognostic nutritional index, tumor-infiltrating lymphocytes, and prognosis in patients with esophageal cancer","volume":"271","author":"Okadome","year":"2020","journal-title":"Ann Surg"},{"key":"2026041706064877200_uxag018-B4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/s41577-019-0221-9","article-title":"Defining \u2018T cell exhaustion\u2019","volume":"19","author":"Blank","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"2026041706064877200_uxag018-B5","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.immuni.2015.01.006","article-title":"The transcription factor NFAT promotes exhaustion of activated CD8+ T cells","volume":"42","author":"Martinez","year":"2015","journal-title":"Immunity"},{"key":"2026041706064877200_uxag018-B6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"Tox transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"2026041706064877200_uxag018-B7","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1152\/physrev.00035.2007","article-title":"Evolution and function of the ADP ribosyl cyclase\/CD38 gene family in physiology and pathology","volume":"88","author":"Malavasi","year":"2008","journal-title":"Physiol Rev"},{"key":"2026041706064877200_uxag018-B8","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat Immunol"},{"key":"2026041706064877200_uxag018-B9","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"2026041706064877200_uxag018-B10","doi-asserted-by":"crossref","first-page":"11398","DOI":"10.1128\/JVI.01177-06","article-title":"PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion","volume":"80","author":"Urbani","year":"2006","journal-title":"J Virol"},{"key":"2026041706064877200_uxag018-B11","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1182\/blood-2008-12-195792","article-title":"Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired","volume":"114","author":"Ahmadzadeh","year":"2009","journal-title":"Blood"},{"key":"2026041706064877200_uxag018-B12","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1084\/jem.20100643","article-title":"Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity","volume":"207","author":"Sakuishi","year":"2010","journal-title":"J Exp Med"},{"key":"2026041706064877200_uxag018-B13","doi-asserted-by":"crossref","first-page":"1182016","DOI":"10.3389\/fimmu.2023.1182016","article-title":"CD38 marks the exhausted CD8+ tissue-resident memory T cells in hepatocellular carcinoma","volume":"14","author":"Reolo","year":"2023","journal-title":"Front Immunol"},{"key":"2026041706064877200_uxag018-B14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.4049\/jimmunol.170.1.477","article-title":"Ablation of CD8 and CD4 T cell responses by high viral loads","volume":"170","author":"Fuller","year":"2003","journal-title":"J Immunol"},{"key":"2026041706064877200_uxag018-B15","doi-asserted-by":"crossref","first-page":"4204","DOI":"10.4049\/jimmunol.172.7.4204","article-title":"Maintenance, loss, and resurgence of T cell responses during acute, protracted, and chronic viral infections","volume":"172","author":"Fuller","year":"2004","journal-title":"J Immunol"},{"key":"2026041706064877200_uxag018-B16","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/intimm\/dxaf002","article-title":"Cancer immunotherapy in progress\u2014an overview of the past 130 years","volume":"37","author":"Ikeda","year":"2025","journal-title":"Int Immunol"},{"key":"2026041706064877200_uxag018-B17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41467-022-35238-w","article-title":"A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer","volume":"14","author":"Tietscher","year":"2023","journal-title":"Nat Commun"},{"key":"2026041706064877200_uxag018-B18","first-page":"3147","article-title":"The story of MCF-7 breast cancer cell line: 40 years of experience in research","volume":"35","author":"Com\u015fa","year":"2015","journal-title":"Anticancer Res"},{"key":"2026041706064877200_uxag018-B19","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1073\/pnas.40.10.1014","article-title":"A nerve growth-stimulating factor isolated from sarcom as 37 and 180","volume":"40","author":"Cohen","year":"1954","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026041706064877200_uxag018-B20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10549-019-05341-6","article-title":"\u03b2 2-adrenergic receptor expression is associated with biomarkers of tumor immunity and predicts poor prognosis in estrogen receptor-negative breast cancer","volume":"177","author":"Kurozumi","year":"2019","journal-title":"Breast Cancer Res Treat"},{"key":"2026041706064877200_uxag018-B21","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5483\/BMBRep.2015.48.5.008","article-title":"Adrenergic receptor \u03b22 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment","volume":"48","author":"Qin","year":"2015","journal-title":"BMB Rep"},{"key":"2026041706064877200_uxag018-B22","doi-asserted-by":"crossref","first-page":"1236361","DOI":"10.1126\/science.1236361","article-title":"Autonomic nerve development contributes to prostate cancer progression","volume":"341","author":"Magnon","year":"2013","journal-title":"Science"},{"key":"2026041706064877200_uxag018-B23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbi.2014.02.019","article-title":"Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment","volume":"40","author":"Kim-Fuchs","year":"2014","journal-title":"Brain Behav Immun"},{"key":"2026041706064877200_uxag018-B24","doi-asserted-by":"crossref","first-page":"5639","DOI":"10.1158\/0008-5472.CAN-17-0546","article-title":"\u03b2-Adrenergic signaling in mice housed at standard temperatures suppresses an effector phenotype in CD8+ T cells and undermines checkpoint inhibitor therapy","volume":"77","author":"Bucsek","year":"2017","journal-title":"Cancer Res"},{"key":"2026041706064877200_uxag018-B25","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1158\/2326-6066.CIR-20-0445","article-title":"Chronic adrenergic stress contributes to metabolic dysfunction and an exhausted phenotype in T cells in the tumor microenvironment","volume":"9","author":"Qiao","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"2026041706064877200_uxag018-B26","doi-asserted-by":"crossref","first-page":"e71980","DOI":"10.1371\/journal.pone.0071980","article-title":"The \u03b2-blocker nebivolol is a GRK\/\u03b2-arrestin biased agonist","volume":"8","author":"Erickson","year":"2013","journal-title":"PloS one"},{"key":"2026041706064877200_uxag018-B27","doi-asserted-by":"crossref","first-page":"1446424","DOI":"10.3389\/fimmu.2024.1446424","article-title":"The \u03b22-adrenergic biased agonist nebivolol inhibits the development of Th17 and the response of memory Th17 cells in an NF-\u03baB-dependent manner","volume":"15","author":"Hajiaghayi","year":"2024","journal-title":"Front Immunol"},{"key":"2026041706064877200_uxag018-B28","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3934\/Allergy.2021017","article-title":"Modulation of IL-17A and IFN\u03b3 by \u03b22-adrenergic agonist terbutaline and inverse-agonist nebivolol, influence of ADRB2 polymorphisms","volume":"5","author":"Gonczi","year":"2021","journal-title":"AIMS Allergy Immunol"},{"key":"2026041706064877200_uxag018-B29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/cyto.a.24496","article-title":"Single cell multiomic analysis of T cell exhaustion in vitro","volume":"101","author":"Corselli","year":"2022","journal-title":"Cytometry Part A"},{"key":"2026041706064877200_uxag018-B30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-0716-0171-6_6","volume-title":"Immuno-oncology: cellular and translational approaches","author":"Dunsford","year":"2020"},{"key":"2026041706064877200_uxag018-B31","doi-asserted-by":"crossref","first-page":"eade3369","DOI":"10.1126\/sciimmunol.ade3369","article-title":"In vitro modeling of CD8+ T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40","volume":"8","author":"Wu","year":"2023","journal-title":"Sci Immunol"},{"key":"2026041706064877200_uxag018-B32","doi-asserted-by":"crossref","first-page":"e1008555","DOI":"10.1371\/journal.ppat.1008555","article-title":"Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by TCF7 promotor methylation","volume":"16","author":"Zhao","year":"2020","journal-title":"PLoS Pathog"},{"key":"2026041706064877200_uxag018-B33","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.191220","article-title":"Faithful modeling of terminal CD8+T cell dysfunction and epigenetic stabilization in vitro","volume":"10","author":"Yousif","year":"2025","journal-title":"JCI Insight"},{"key":"2026041706064877200_uxag018-B34","doi-asserted-by":"crossref","first-page":"101954","DOI":"10.1016\/j.xpro.2022.101954","article-title":"Inducing T cell dysfunction by chronic stimulation of CAR-engineered T cells targeting cancer cells in suspension cultures","volume":"4","author":"Selli","year":"2023","journal-title":"STAR Protoc"},{"key":"2026041706064877200_uxag018-B35","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"2026041706064877200_uxag018-B36","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1073\/pnas.0610335104","article-title":"Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection","volume":"104","author":"Agnellini","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026041706064877200_uxag018-B37","doi-asserted-by":"crossref","first-page":"e153963","DOI":"10.1172\/jci.insight.153963","article-title":"Tumor-infiltrating exhausted CD8+ T cells dictate reduced survival in premenopausal estrogen receptor\u2013positive breast cancer","volume":"7","author":"Egelston","year":"2022","journal-title":"JCI Insight"},{"key":"2026041706064877200_uxag018-B38","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2018.11.043","article-title":"Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma","volume":"176","author":"Li","year":"2019","journal-title":"Cell"},{"key":"2026041706064877200_uxag018-B39","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1084\/jem.20150598","article-title":"High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival","volume":"213","author":"Utzschneider","year":"2016","journal-title":"J Exp Med"},{"key":"2026041706064877200_uxag018-B40","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/s41590-020-0725-2","article-title":"Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen","volume":"21","author":"Vardhana","year":"2020","journal-title":"Nat Immunol"},{"key":"2026041706064877200_uxag018-B41","doi-asserted-by":"crossref","first-page":"jcs259481","DOI":"10.1242\/jcs.259481","article-title":"Trf2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection","volume":"135","author":"Nguyen","year":"2022","journal-title":"J Cell Sci"},{"key":"2026041706064877200_uxag018-B42","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1158\/1078-0432.CCR-17-1846","article-title":"T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma","volume":"24","author":"Woroniecka","year":"2018","journal-title":"Clin Cancer Res"},{"key":"2026041706064877200_uxag018-B43","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/j.1365-2567.2010.03255.x","article-title":"T-cell exhaustion: characteristics, causes and conversion","volume":"129","author":"Yi","year":"2010","journal-title":"Immunology"},{"key":"2026041706064877200_uxag018-B44","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3389\/fimmu.2018.00164","article-title":"Adrenergic signaling: a targetable checkpoint limiting development of the antitumor immune response","volume":"9","author":"Qiao","year":"2018","journal-title":"Front Immunol"},{"key":"2026041706064877200_uxag018-B45","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00262-014-1617-9","article-title":"A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response","volume":"63","author":"Eng","year":"2014","journal-title":"Cancer Immunol Immunother"},{"key":"2026041706064877200_uxag018-B46","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s10549-011-1348-y","article-title":"\u03b2-Adrenergic receptors (\u03b2-AR) regulate VEGF and IL-6 production by divergent pathways in high \u03b2-AR-expressing breast cancer cell lines","volume":"130","author":"Madden","year":"2011","journal-title":"Breast Cancer Res Treat"},{"key":"2026041706064877200_uxag018-B47","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/s41419-019-2030-2","article-title":"Chronic stress promotes gastric cancer progression and metastasis: an essential role for ADRB2","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis"},{"key":"2026041706064877200_uxag018-B48","doi-asserted-by":"crossref","first-page":"756","DOI":"10.2174\/1568009617666170330151415","article-title":"The \u03b2 2-adrenergic agonist salbutamol inhibits migration, invasion and metastasis of the human breast cancer MDA-MB-231 cell line","volume":"17","author":"Rivero","year":"2017","journal-title":"Curr Cancer Drug Targets"},{"key":"2026041706064877200_uxag018-B49","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.3892\/or.2016.4710","article-title":"Inhibition of \u03b22-adrenergic receptor reduces triple-negative breast cancer brain metastases: the potential benefit of perioperative \u03b2-blockade","volume":"35","author":"Choy","year":"2016","journal-title":"Oncol Rep"},{"key":"2026041706064877200_uxag018-B50","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1002\/eji.201646395","article-title":"Sympathetic neural signaling via the \u03b22-adrenergic receptor suppresses T-cell receptor-mediated human and mouse CD8+ T-cell effector function","volume":"46","author":"Estrada","year":"2016","journal-title":"Eur J Immunol"},{"key":"2026041706064877200_uxag018-B51","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jaci.2005.11.012","article-title":"Molecular mechanisms of \u03b22-adrenergic receptor function, response, and regulation","volume":"117","author":"Johnson","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"2026041706064877200_uxag018-B52","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.3390\/ijms24065894","article-title":"Blockade of \u03b2-adrenergic receptors by nebivolol enables tumor control potential for uveal melanoma in 3D tumor spheroids and 2D cultures","volume":"24","author":"Farhoumand","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026041706064877200_uxag018-B53","doi-asserted-by":"crossref","first-page":"691998","DOI":"10.3389\/fphar.2021.691998","article-title":"Adrenergic blockade by nebivolol to suppress oral squamous cell carcinoma growth via endoplasmic reticulum stress and mitochondria dysfunction","volume":"12","author":"Chen","year":"2021","journal-title":"Front Pharmacol"},{"key":"2026041706064877200_uxag018-B54","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3390\/ijms21020512","article-title":"\u03b2-blockers reverse agonist-induced \u03b22-AR downregulation regardless of their signaling profile","volume":"21","author":"Maccari","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026041706064877200_uxag018-B55","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s10571-010-9540-x","article-title":"Repeated stress down-regulates \u03b22-and \u03b12C-adrenergic receptors and up-regulates gene expression of IL-6 in the rat spleen","volume":"30","author":"Laukova","year":"2010","journal-title":"Cell Mol Neurobiol"},{"key":"2026041706064877200_uxag018-B56","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1074\/jbc.273.6.3223","article-title":"Agonist regulation of human \u03b22-adrenergic receptor mRNA stability occurs via a specific AU-rich element","volume":"273","author":"Danner","year":"1998","journal-title":"J Biol Chem"},{"key":"2026041706064877200_uxag018-B57","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/s41590-023-01529-7","article-title":"The GPCR\u2013G\u03b1s\u2013PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure","volume":"24","author":"Wu","year":"2023","journal-title":"Nat Immunol"},{"key":"2026041706064877200_uxag018-B58","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.bbi.2010.07.248","article-title":"Stimulation of \u03b22-adrenergic receptors inhibits calcineurin activity in CD4+ T cells via PKA\u2013AKAP interaction","volume":"25","author":"Riether","year":"2011","journal-title":"Brain Behav Immun"},{"key":"2026041706064877200_uxag018-B59","doi-asserted-by":"crossref","first-page":"12912","DOI":"10.1073\/pnas.91.26.12912","article-title":"Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop","volume":"91","author":"Bergquist","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026041706064877200_uxag018-B60","doi-asserted-by":"crossref","first-page":"109905","DOI":"10.1016\/j.cellsig.2020.109905","article-title":"Biased agonism at \u03b2-adrenergic receptors","volume":"80","author":"Ippolito","year":"2021","journal-title":"Cell Signal"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cei\/advance-article-pdf\/doi\/10.1093\/cei\/uxag018\/67641498\/uxag018.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/220\/1\/uxag018\/68104231\/uxag018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/220\/1\/uxag018\/68104231\/uxag018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:07:09Z","timestamp":1776420429000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/doi\/10.1093\/cei\/uxag018\/8556682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/cei\/uxag018","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"uxag018"}}