title: Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin and B-cell lymphomas.
abstract: Activation of the programmed death 1 (PD1)/PD1 ligand (PDL1) pathway is important for tumor cells to escape from immune control. The clinical efficacy of therapeutic modulation of the PD1-PDL1 pathway has been recently shown in classical Hodgkin lymphoma (cHL), but little is known about the frequency and diagnostic and prognostic importance of PDL1 expression in lymphomas. The available anti-PDL1 antibody clones E1L3N and SP142 were compared, and a large cohort of Hodgkin lymphomas (n=280) and B-cell lymphomas (n=619) was examined for PDL1 using E1L3N. The results were correlated with the expression of other phenotypic markers, interphase fluorescence in situ hybridization data of the 9p24.1 region (PDL1 locus), and the clinical outcome. PDL1 was expressed on more than 5% of tumor cells in 70% of cHL, 54% of nodular lymphocyte-predominant Hodgkin lymphoma, and 35% of primary mediastinal B-cell lymphomas; in the latter, PDL1 expression correlated with PDL1 gains (ρ=0.573). PDL1 was expressed in 31% of primary diffuse large B-cell lymphomas (DLBCLs), whereas most other entities did not express PDL1. In cHL, expression of PDL1 correlated with increased numbers of granzyme+ T cells (ρ=0.251) and CD68+ macrophages (ρ=0.221) but with decreased numbers of FoxP3+ T cells (ρ=0.145). In activated B-cell-like DLBCL, PDL1 positively correlated with PD1+ T cells, whereas an inverse correlation with FoxP3+ T cells was seen in the germinal center B-cell-like DLBCL. PDL1 expression can be diagnostically valuable in some gray zones around DLBCL and cHL; it identifies an "immune escape" cluster of cHL and activated B-cell-like DLBCL with increased granzyme+ and PD1+ T cells and macrophages and decreased regulatory T cells.
authors.affiliation: Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland; Department of Histopathology, Hammersmith Hospital Campus, Imperial College Healthcare NHS Trust, W12 0HS London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Menter
authors.affiliation: Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bodmer-Haecki
authors.affiliation: Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.affiliation: Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland. Electronic address: alexandar.tzankov@usb.ch.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D060890:B7-H1 Antigen / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D018572:Disease-Free Survival; D051858:Forkhead Transcription Factors / Q000032:analysis; D053804:Granzymes / Q000032:analysis; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000737:chemistry; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000737:chemistry; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D053804:Granzymes; C423236:CD274 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C418974:FOXP3 protein, human
keywords: B-cell lymphoma; Diagnostic marker; Hodgkin lymphoma; Immunohistochemistry; PDL1