{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:53:32Z","timestamp":1791420812307,"version":"4.3.3"},"reference-count":37,"publisher":"European Respiratory Society (ERS)","issue":"4","funder":[{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS)-Fondos FEDER","award":["PI13\/01512"],"award-info":[{"award-number":["PI13\/01512"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS)-Fondos FEDER","award":["PI14\/00004"],"award-info":[{"award-number":["PI14\/00004"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS)-Fondos FEDER","award":["PI14\/01234"],"award-info":[{"award-number":["PI14\/01234"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria (FIS)-Fondos FEDER","award":["PIE15\/00065"],"award-info":[{"award-number":["PIE15\/00065"]}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2017,7,23]]},"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8<jats:sup>+<\/jats:sup>T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human<jats:italic>in vitro<\/jats:italic>and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1\u03b1 transfection. PD-L1\/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8<jats:sup>+<\/jats:sup>T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1\/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8<jats:sup>+<\/jats:sup>T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.<\/jats:p>","DOI":"10.1183\/13993003.00833-2017","type":"journal-article","created":{"date-parts":[[2017,10,20]],"date-time":"2017-10-20T10:38:48Z","timestamp":1508495928000},"page":"1700833","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":102,"title":["Hypoxia-induced PD-L1\/PD-1 crosstalk impairs T-cell function in sleep apnoea"],"prefix":"10.1183","volume":"50","author":[{"given":"Carolina","family":"Cubillos-Zapata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Avenda\u00f1o-Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2478-2700","authenticated-orcid":false,"given":"Enrique","family":"Hernandez-Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Toledano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Casas-Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anibal","family":"Varela-Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Almendros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Casitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Fern\u00e1ndez-Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldara","family":"Garcia-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-9385","authenticated-orcid":false,"given":"Luis A.","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Farre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"L\u00f3pez-Collazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Garc\u00eda-Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2017,10,19]]},"reference":[{"key":"2024101904275854000_50.4.1700833.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00043-0"},{"key":"2024101904275854000_50.4.1700833.2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201201-0130OC"},{"key":"2024101904275854000_50.4.1700833.3","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1671OC"},{"key":"2024101904275854000_50.4.1700833.4","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00115413"},{"key":"2024101904275854000_50.4.1700833.5","doi-asserted-by":"crossref","first-page":"e0152749","DOI":"10.1371\/journal.pone.0152749","article-title":"Association between obstructive sleep apnea and community-acquired pneumonia","volume":"11","author":"Chiner","year":"2016","journal-title":"PLoS One"},{"key":"2024101904275854000_50.4.1700833.6","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00127912"},{"key":"2024101904275854000_50.4.1700833.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1514296"},{"key":"2024101904275854000_50.4.1700833.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00923.x"},{"key":"2024101904275854000_50.4.1700833.9","doi-asserted-by":"publisher","DOI":"10.1038\/nm730"},{"key":"2024101904275854000_50.4.1700833.10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195792"},{"key":"2024101904275854000_50.4.1700833.11","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv615"},{"key":"2024101904275854000_50.4.1700833.12","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506"},{"key":"2024101904275854000_50.4.1700833.13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ccell.2015.07.006","article-title":"RORC1 regulates tumor-promoting \u201cemergency\u201d granulo-monocytopoiesis","volume":"28","author":"Strauss","year":"2015","journal-title":"Cancer Cell"},{"key":"2024101904275854000_50.4.1700833.14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ccell.2015.07.007","article-title":"ROR1C regulates differentiation of myeloid-derived suppressor cells","volume":"28","author":"Gabrilovich","year":"2015","journal-title":"Cancer Cell"},{"key":"2024101904275854000_50.4.1700833.15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916"},{"key":"2024101904275854000_50.4.1700833.16","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.chest.2015.11.010","article-title":"Intermittent hypoxia-induced cardiovascular remodeling is reversed by normoxia in a mouse model of sleep apnea","volume":"149","author":"Castro-Graffoni","year":"2016","journal-title":"Chest"},{"key":"2024101904275854000_50.4.1700833.17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.556746"},{"key":"2024101904275854000_50.4.1700833.18","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02456-2016"},{"key":"2024101904275854000_50.4.1700833.19","doi-asserted-by":"crossref","first-page":"e954463","DOI":"10.4161\/21624011.2014.954463","article-title":"Targeting hypoxia at the forefront of anticancer immune responses","volume":"3","author":"Noman","year":"2015","journal-title":"Oncoimmunology"},{"key":"2024101904275854000_50.4.1700833.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061602"},{"key":"2024101904275854000_50.4.1700833.21","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00007008"},{"key":"2024101904275854000_50.4.1700833.22","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.immuni.2016.10.008","article-title":"Immunomodulatory functions of BTLA and HVEM govern induction of extrathymic regulatory T cells and tolerance by dendritic cells","volume":"45","author":"Jones","year":"2016","journal-title":"Immunity"},{"key":"2024101904275854000_50.4.1700833.23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4696"},{"key":"2024101904275854000_50.4.1700833.24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00109-003-0430-2","article-title":"B7-H1 pathway and its role in the evasion of tumor immunity","volume":"81","author":"Dong","year":"2003","journal-title":"J Mol Med"},{"key":"2024101904275854000_50.4.1700833.25","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3259"},{"key":"2024101904275854000_50.4.1700833.26","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2703"},{"key":"2024101904275854000_50.4.1700833.27","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1679"},{"key":"2024101904275854000_50.4.1700833.28","doi-asserted-by":"crossref","first-page":"e28581","DOI":"10.4161\/onci.28581","article-title":"Myeloid-derived suppressor cells link inflammation to cancer","volume":"3","author":"Wang","year":"2014","journal-title":"Oncoimmunology"},{"key":"2024101904275854000_50.4.1700833.29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100587"},{"key":"2024101904275854000_50.4.1700833.30","doi-asserted-by":"crossref","first-page":"35651","DOI":"10.1038\/srep35651","article-title":"PD-L1 is a critical mediator of regulatory B cells and T cells in invasive breast cancer","volume":"6","author":"Guan","year":"2016","journal-title":"Sci Rep"},{"key":"2024101904275854000_50.4.1700833.31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00262-016-1936-0","article-title":"A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1 and is associated with PD-L1 overexpression and increased occurrence of gastric cancer","volume":"66","author":"Tao","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"2024101904275854000_50.4.1700833.32","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24899"},{"key":"2024101904275854000_50.4.1700833.33","doi-asserted-by":"crossref","first-page":"e0162925","DOI":"10.1371\/journal.pone.0162925","article-title":"Elevated cellular PD1\/PD-L1 expression confers acquired resistance to cisplatin in small cell lung cancer cells","volume":"11","author":"Yan","year":"2016","journal-title":"PLoS One"},{"key":"2024101904275854000_50.4.1700833.34","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252510"},{"key":"2024101904275854000_50.4.1700833.35","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201310-1830OC"},{"key":"2024101904275854000_50.4.1700833.36","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0782OC"},{"key":"2024101904275854000_50.4.1700833.37","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02851-13"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.00833-2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:45:02Z","timestamp":1740379502000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.00833-2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,10,19]]},"published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1183\/13993003.00833-2017"],"URL":"https:\/\/doi.org\/10.1183\/13993003.00833-2017","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]}}}