Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders

Am J Surg Pathol. 2016 Apr;40(4):443-53. doi: 10.1097/PAS.0000000000000590.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers / analysis
  • Female
  • Histiocytic Necrotizing Lymphadenitis / metabolism*
  • Histiocytosis, Langerhans-Cell / metabolism*
  • Histiocytosis, Sinus / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Ligand 2 Protein / biosynthesis*
  • Sarcoidosis / metabolism*


  • B7-H1 Antigen
  • Biomarkers
  • CD274 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein