title: PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies.
abstract: OBJECTIVE
  Programmed cell death ligand 1 (PD-L1) is an immunomodulatory molecule expressed by antigen-presenting cells and select tumors that engages receptors on T cells to inhibit T-cell immunity. Immunotherapies targeting the PD-1/PD-L1 pathway have shown durable antitumor effects in a subset of patients with solid tumors. PD-L1 can be expressed by Reed-Sternberg cells comprising classical Hodgkin lymphoma (CHL) and by malignant B cells comprising EBV-positive posttransplant lymphoproliferative disorders (PTLD). We sought to determine whether the expression of PD-L1 represents a general strategy of immune evasion among aggressive B-cell lymphomas and virus- and immunodeficiency-associated tumors.
  
  
  METHODS
  Using novel antibodies and formalin-fixed, paraffin-embedded (FFPE) tissue biopsies, we examined 237 primary tumors for expression of PD-L1.
  
  
  RESULTS
  Robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1.
  
  
  CONCLUSIONS
  Certain aggressive B-cell lymphomas and virus- and immunodeficiency-associated malignancies associated with an ineffective T-cell immune response express PD-L1 on tumor cells and infiltrating macrophages. These results identify a group of neoplasms that should be considered for PD-1/PD-L1-directed therapies, and validate methods to detect PD-L1 in FFPE tissue biopsies.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Chen
authors.forename: Bjoern
authors.initials: B
authors.lastname: Chapuy
authors.forename: Jing
authors.initials: J
authors.lastname: Ouyang
authors.forename: Heather H
authors.initials: HH
authors.lastname: Sun
authors.forename: Margaretha G M
authors.initials: MG
authors.lastname: Roemer
authors.forename: Mina L
authors.initials: ML
authors.lastname: Xu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yu
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Shipp
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000472:pathogenicity; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology*
chemical_list: D060890:B7-H1 Antigen