Increased Expression of PD‐1 and PD‐L1 in Patients With Laryngotracheal Stenosis. (17th June 2020)

• Record Type: Journal Article
• Authors: Davis, Ruth J.; Lina, Ioan; Ding, Dacheng; Engle, Elizabeth L.; Taube, Janis; Gelbard, Alexander; Hillel, Alexander T.
• Is Part Of: Laryngoscope. Volume 131:Number 5(2021)
• Page Start: 967
• Page End: 974
• Publication Date: 2020-06-17
• Subjects: Laryngotracheal stenosis -- PD‐1 -- PD‐L1 -- T lymphocytes; Otolaryngology -- Periodicals; 617.51005
• DOI: 10.1002/lary.28790
• Languages: English
• ISSNs: 0023-852X

Abstract

Abstract : Objectives: 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‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis, targeted by paradigm‐shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD‐1/PD‐L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored. Study Design: Controlled ex vivo study. Methods: Expression of PD‐1, PD‐L1, 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 (TGFβ1) and analyzed for PD‐L1 expression by quantitative real‐time polymerase chain reaction (n = 6). Results: iLTS specimens exhibited increased expression of PD‐1, PD‐L1, and CD4 (all P < .0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD‐1 and CD4 ( P < .0167) compared to controls. PD‐1, PD‐L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGFβ1 treatment of iLTS fibroblasts increased expression of PD‐L1 (the cognate ligand for PD‐1). Conclusion: Expression of both PD‐1 and its ligand PD‐L1 are significantly greater in patients with iLTS compared to controls, and PD‐1 expression is also elevated in patients with iSGS. Given published evidence implicating the PD‐1/PD‐L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD‐1/PD‐L1 axis for the treatment of LTS. Level of Evidence: N/A Laryngoscope, 131:967–974, 2021