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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
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Saint Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
SydPath, Saint Vincent’s Hospital, Sydney, Australia
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Gene & Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia
Faculty of Medicine & Health, The University of Sydney, Camperdown, New South Wales, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
School of Medicine, University of Wollongong, New South Wales, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
Department of Head & Neck Surgery, Liverpool Hospital, Liverpool, New South Wales, Australia
Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
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School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
South West Sydney Clinical School, UNSW Sydney, Sydney, Australia
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Programmed cell death-ligand 1 (PD-L1) has recently been shown to play a role in the regulation of epithelial-to-mesenchymal transition (EMT); however, the relationship between PD-L1 expression, EMT and the inflammatory tumour microenvironment has yet to be investigated in thyroid cancer. To address this issue, we examined the expression of CD8, PD-L1 and the EMT markers E-cadherin and vimentin in a cohort of 74 papillary thyroid cancer (PTC) patients and investigated the association of these with clinicopathologic characteristics and disease-free survival (DFS). The relationship between PD-L1 and EMT was further examined in three thyroid cancer cell lines via Western blot and live cell imaging. In order to expand our in vitro findings, the normalised gene expression profiles of 516 thyroid cancer patients were retrieved and analysed from The Cancer Genome Atlas (TCGA). PD-L1 positivity was significantly higher in PTC patients exhibiting a mesenchymal phenotype (P = 0.012). Kaplan–Meier analysis revealed that PD-L1 (P = 0.045), CD8 (P = 0.038) and EMT status (P = 0.038) were all significant predictors for DFS. Sub-analysis confirmed that the poorest DFS was evident in PD-L1 positive patients with EMT features and negative CD8 expression (P < 0.0001). IFN-γ treatment induced upregulation of PD-L1 and significantly promoted an EMT phenotype in two thyroid cancer cell lines. Our findings suggest that PD-L1 signalling may play a role in stimulating EMT in thyroid cancer. EMT, CD8 and PD-L1 expression may serve as valuable predictive biomarkers in patients with PTC.
