title: Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders.
abstract: Programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2) are cell surface proteins expressed by activated antigen-presenting cells and by select malignancies that bind PD-1 on T cells to inhibit immune responses. Antibodies targeting PD-1 or PD-L1 elicit antitumor immunity in a subset of patients, and clinical response correlates with PD-1 ligand expression by malignant or immune cells within the tumor microenvironment. We examined the expression of PD-1 ligands on subsets of antigen-presenting cells and 87 histiocytic and dendritic cell disorders including those that are benign, borderline, and malignant. Within reactive lymphoid tissue, strong PD-L1 is detected on most macrophages, subsets of interdigitating dendritic cells, and plasmacytoid dendritic cells, but not on follicular dendritic cells or Langerhans cells. Macrophage/dendritic cell subsets do not express discernible PD-L2. Seven of 7 cases of sarcoidosis (100%), 6 of 6 cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) (100%), 2 of 11 cases of Rosai-Dorfman disease (18%), and 3 of 15 cases of Langerhans cell histiocytosis (20%) exhibited positivity for PD-L1. All cases of sarcoidosis were also positive for PD-L2. Seven of 14 histiocytic sarcomas (50%), 2 of 5 interdigitating dendritic cell sarcomas (40%), 10 of 20 follicular dendritic cell sarcomas (50%), and none of 9 blastic plasmacytoid dendritic cell neoplasms were positive for PD-L1. Eleven of 20 (55%) follicular dendritic cell sarcomas were also positive for PD-L2. PD-L1 and PD-L2 are useful new markers for identifying select histiocyte and dendritic cell disorders and reveal novel patient populations as rational candidates for immunotherapy.
authors.affiliation: *Department of Pathology, Brigham and Women's Hospital Departments of †Medical Oncology ‡Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Heather H
authors.initials: HH
authors.lastname: Sun
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Morgan
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D020042:Histiocytic Necrotizing Lymphadenitis / Q000378:metabolism*; D006646:Histiocytosis, Langerhans-Cell / Q000378:metabolism*; D015618:Histiocytosis, Sinus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis*; D012507:Sarcoidosis / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein