Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot study

• Main Authors: Larson, A. (Author), Lerman, M. (Author), Motta, A.C.F (Author), Murphy, G.F (Author), Soiffer, R.J (Author), Treister, N.S (Author), Woo, S.-B (Author), Zhan, Q. (Author)
• Format: Article
• Language: English
• Published: Blackwell Publishing Ltd 2018
• Subjects: Administration, Topical; adult; Adult; aged; Aged; Antigens, CD; apoptosis; Article; biomarkers; CD103 antigen; CD163 antigen; CD20 antigen; CD3 antigen; CD4 antigen; CD8 antigen; cell infiltration; chronic graft versus host disease; chronic graft-versus-host disease; chronic lymphatic leukemia; chronic myeloid leukemia; clinical article; controlled study; dexamethasone; Dexamethasone; exocytosis; female; Female; forkhead transcription factor; Forkhead Transcription Factors; FOXP3 protein, human; glucocorticoid; Glucocorticoids; graft versus host reaction; Graft vs Host Disease; histopathology; human; human tissue; Humans; immunohistochemistry; Immunohistochemistry; immunology; immunomodulation; Immunomodulation; immunopathology; immunosuppressive agent; Immunosuppressive Agents; immunosuppressive treatment; leukocyte antigen; lichenoid; macrophage; Macrophages; male; Male; mast cell; metabolism; middle aged; Middle Aged; mouth disease; Mouth Diseases; myelodysplastic syndrome; myeloproliferative disorder; neutrophil; nonhodgkin lymphoma; oral biopsy; oral mucosa; PADGEM protein; pathology; peripheral blood stem cell transplantation; pilot study; platelet endothelial cell adhesion molecule 1; prednisone; priority journal; rapamycin; sclerosis; stem cell factor receptor; T lymphocyte; t6 antigen; tacrolimus; Tacrolimus; T-Lymphocytes; topical drug administration; topical therapy; transcription factor FOXP3; young adult; Young Adult
• Online Access: View Fulltext in Publisher

 Objective: To characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. Material and Methods: Paired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5). Results: Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+, CD4+, CD8+, CD103+, CD163+, and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells. Conclusion: The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.