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A7677 - PD-L1 Expression in IPF Tissue Samples
Author Block: D. Jovanovic1, J. Markovic1, S. Glumac2, S. Skodric-Radojevic2, V. Skodric-Trifunovic1, M. Roksandic-Milenkovic1, I. Vukanic1, S. Popevic1, N. Samardzic1, M. Kontic1, V. Ceriman1; 1University Hospital of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia, 2Institute for Pathology, Faculty of Medicine, Belgrade, Serbia.
Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) that involves alterations in innate inflammatory cells, epithelial cells, and fibroblasts with macrophages acquiring a phenotype which promotes fibroproliferation (‘pro-fibrotic’ macrophages), producing various mediators that directly activate fibroblasts and the proliferation of myofibroblasts. There are striking similarities in the pathobiology and clinical outcomes of IPF and lung cancer. PD-1 plays a role in controlling inflammatory response to injury in the normal lung tissues and could be critical in the pathogenesis of both IPF and lung cancer. Monocytes and macrophages serve as antigen-presenting cells (APCs) and deliver costimulatory and coinhibitory signals to interacting T cells. Macrophages are key regulators of lung fibrosis. Alveolar macrophages acting as APCs, promote Th2 responses, but they can also suppress T cell immunity by expressing immuno-inhibitory ligands, such as programmed death ligand-1 (PD-L1). In a recently published study, RNA sequencing pointed to CD274 as significantly downregulated gene in human IPF lung tissue. The aim of this study was to explore PD-L1 expression in formalin-fixed, paraffin-embedded human IPF lung tissue samples, and to delineate cells with PD-L1 expression. Methods: IHH analysis (clone 22C3) of human IPF lung tissue samples from 12 patients. Results: PD-L1 expression in IPF alveolar macrophages was negative in 3 cases, but there was positivity to overexpression of PD-L1 in 9 IPF cases. Only very few cells in the interstitium have shown discrete PD-L1 expression, but non of a membrane type. Conclusion: IPF with alveolar macrophages PD-L1 overexpression might be a specific IPF Phenotype, or just an IPF development Phase. Many questions raise from similarities in the pathobiology of IPF and lung cancer. Based on these similarities and common expression of a number of GFs, some lung cancer drugs have already been translated into treatment option for IPF (Nintedanib). For IPF with alveolar macrophages PD-L1 overexpression, we might raise a question if there a place to investigate some new treatment modalities or combinations as well.