title: Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells.
abstract: OBJECTIVE
  Programmed death ligand 1 (PD-L1) is expressed on antigen-presenting cells and inhibits activation of T cells through its receptor PD-1. PD-L1 is aberrantly expressed on some epithelial malignancies and Hodgkin lymphomas and may prevent effective host antitumor immunity. The role of PD-L1 in non-Hodgkin lymphomas (NHL) is not well characterized.
  
  
  METHODS
  PD-L1 expression was analyzed in cell lines and lymphoma specimens by using flow cytometry and immunohistochemistry. Functional activity of PD-L1 was studied by incubating irradiated lymphoma cells with allogeneic T cells with or without anti-PD-L1 blocking antibody; T-cell proliferation and IFN-γ secretion served as measures of T-cell activation. Similar experiments were conducted using cultures of primary lymphoma specimens containing host T cells.
  
  
  RESULTS
  PD-L1 was expressed uniformly by anaplastic large cell lymphoma (ALCL) cell lines, but rarely in B-cell NHL, confined to a subset of diffuse large B-cell lymphomas (DLBCL) with activated B-cell features (3 of 28 cell lines and 24% of primary DLBCL). Anti-PD-L1 blocking antibody boosted proliferation and IFN-γ secretion by allogeneic T cells responding to ALCL and DLBCL cells. In autologous cultures of primary ALCL and DLBCL, PD-L1 blockade enhanced secretion of inflammatory cytokines IFN-γ, granulocyte macrophage colony-stimulating factor, interleukin (IL)-1, IL-6, IL-8, IL-13, TNF-α, and macrophage inflammatory protein-1α. In establishing cell lines from an aggressive PD-L1(+) mature B-cell lymphoma, we also noted that PD-L1 expression could be lost under certain in vitro culture conditions.
  
  
  CONCLUSIONS
  PD-L1 may thwart effective antitumor immune responses and represents an attractive target for lymphoma immunotherapy.
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, and Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Andorsky
authors.forename: Reiko E
authors.initials: RE
authors.lastname: Yamada
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: David J
authors.initials: DJ
authors.lastname: Betting
authors.forename: John M
authors.initials: JM
authors.lastname: Timmerman
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines