title: PD-L1, PD-1, CD4, and CD8 expression in neoplastic and nonneoplastic thymus.
abstract: The checkpoint protein programmed cell death ligand-1 protein (PD-L1) binds to its receptor (PD-1) activating the PD-L1/PD-1 pathway, an important therapeutic target. There is limited information regarding PD-L1 and PD-1 expression in thymic lesions. Sections from nonneoplastic thymi (n = 20), thymomas World Health Organization types A, AB, B1, B2, and B3 (n = 38) and thymic squamous cell carcinoma (n = 8) were stained for PD-L1 (clone SP142; Spring BioScience), PD-1 (MRQ22; Cell Marque), CD4 (clone SPO32; Cell Marque), and CD8 (JCB117; Ventana). Immunoreactivity for each antibody was classified as focal or diffuse and scored as follows: 0, negative; 1%-5%, 1+; 6%-20%, 2+; and >20%, 3+. The proportions of cases expressing PD-L1, PD-1, CD4, and C8 at score ≥1+ were compared by diagnosis, using χ2statistics. PD-L1 was expressed in 90% of nonneoplastic thymi, 92% of thymomas, and 50% of carcinomas, with significantly higher scores (P < .01) in B2 and B3 thymomas and carcinomas than in AB and B1 thymomas; PD-L1 was diffuse in most B2 and B3 thymomas and focal in carcinomas. PD-1 was focally expressed, and mostly with scores 1+, in 55% of nonneoplastic thymi, 63% of thymomas, and 37.5% of carcinomas. CD4+ and CD8+ cells were diffusely distributed with scores 3+ in all lesions other than B3 thymomas and carcinomas. The latter showed CD4+ cells mostly at the interface between neoplastic cells and stroma. PD-L1 and PD-1 are not expressed in similar locations and cellular proportions in thymic lesions, raising a question as to whether the PD-L1/PD-1 pathway is an actionable therapeutic target in these lesions.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048. Electronic address: Alberto.Marchevsky@cshs.org.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marchevsky
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048. Electronic address: Ann.Walts@cshs.org.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Walts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D013945:Thymoma / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D013952:Thymus Hyperplasia / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D013953:Thymus Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: CD8; Cd; PD-1; PD-L1; Thymic neoplasms; Thymus