{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T12:38:59Z","timestamp":1786797539772,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005193","name":"American Academy of Otolaryngology-Head and Neck Surgery","doi-asserted-by":"publisher","award":["Resident Research Grant"],"award-info":[{"award-number":["Resident Research Grant"]}],"id":[{"id":"10.13039\/100005193","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1K23DC014082"],"award-info":[{"award-number":["1K23DC014082"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1R01DC018567"],"award-info":[{"award-number":["1R01DC018567"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R21DC017225"],"award-info":[{"award-number":["R21DC017225"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Laryngotracheal stenosis (LTS) is a fibrotic condition of the upper airway. Recent evidence suggests dysregulated host immunity plays a role in LTS development and progression. The programmed death\u20101 (PD\u20101)\/programmed death\u2010ligand 1 (PD\u2010L1) axis, targeted by paradigm\u2010shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD\u20101\/PD\u2010L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Controlled <jats:italic>ex vivo<\/jats:italic> study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of PD\u20101, PD\u2010L1, CD4, and CD8 were evaluated using immunohistochemical staining of cricotracheal resection specimens from postintubation iatrogenic laryngotracheal stenosis (iLTS), idiopathic subglottic stenosis (iSGS) patients, and normal controls derived from rapid autopsy (n = 8 per group). Fibroblasts derived from iLTS scar were also treated with transforming growth factor beta 1 (TGF\u03b21) and analyzed for PD\u2010L1 expression by quantitative real\u2010time polymerase chain reaction (n = 6).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>iLTS specimens exhibited increased expression of PD\u20101, PD\u2010L1, and CD4 (all <jats:italic>P<\/jats:italic> &lt;\u2009.0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD\u20101 and CD4 (<jats:italic>P<\/jats:italic> &lt;\u2009.0167) compared to controls. PD\u20101, PD\u2010L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGF\u03b21 treatment of iLTS fibroblasts increased expression of PD\u2010L1 (the cognate ligand for PD\u20101).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Expression of both PD\u20101 and its ligand PD\u2010L1 are significantly greater in patients with iLTS compared to controls, and PD\u20101 expression is also elevated in patients with iSGS. Given published evidence implicating the PD\u20101\/PD\u2010L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD\u20101\/PD\u2010L1 axis for the treatment of LTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>N\/A <jats:italic>Laryngoscope<\/jats:italic>, 131:967\u2013974, 2021<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.28790","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T18:54:20Z","timestamp":1592420060000},"page":"967-974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Increased Expression of <scp>PD<\/scp>\u20101 and <scp>PD\u2010L1<\/scp> in Patients With Laryngotracheal Stenosis"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-932X","authenticated-orcid":false,"given":"Ruth J.","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-7312","authenticated-orcid":false,"given":"Ioan","family":"Lina","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth L.","family":"Engle","sequence":"additional","affiliation":[{"name":"Bloomberg\u2010Kimmel Institute for Cancer Immunotherapy  Baltimore MD U.S.A."},{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore MD U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Taube","sequence":"additional","affiliation":[{"name":"Bloomberg\u2010Kimmel Institute for Cancer Immunotherapy  Baltimore MD U.S.A."},{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore MD U.S.A."},{"name":"Department of Oncology Johns Hopkins University School of Medicine  Baltimore MD U.S.A."},{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore MD U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0078-1305","authenticated-orcid":false,"given":"Alexander","family":"Gelbard","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Vanderbilt University School of Medicine  Nashville TN 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