title: PD-L1 Status in Refractory Lymphomas.
abstract: Targeted immunotherapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also been observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas. Tumor samples from 78 patients with therapy resistant lymphomas were immunohistochemically (IHC) investigated for the expression of PD-L1 using two antibody clones (SP142 and SP263, Ventana). Thirteen PD-L1+ cases were further analyzed for gene copy number variations (CNV) by NGS and for PD-L1/JAK2/PD-L2 co-amplification using fluorescent in-situ hybridization assay (FISH). PD-L1 positivity (≥5% positive cancer cells, IHC) was present in 32/77 (42%) and 33/71 cases (46%) using SP142 and SP263 antibodies, respectively. Concordance between the two anti-PD-L1 clones was high with only three (4%) discrepant cases. The strongest and consistent (10/11 cases) expression was observed in cHL and primary mediastinal B-cell lymphomas (3/3). Diffuse large B-cell lymphomas (DLBCL) were frequently positive (13/26) irrespective of subtype. Follicular (1/8), peripheral T-cell (3/11) and mantle cell (1/8) lymphomas were rarely positive, while small lymphocytic lymphoma/CLL and marginal zone lymphomas were consistently negative (3/3). Co-amplification/CNVs of PD-L1/JAK2/PD-L2 were observed in 3 cases of DLBCL and cHL, respectively. Of note, all three cHL-amplified cases were positive by FISH, but not by NGS. Since only a fraction of the IHC positive lymphoma cases were positive by FISH and NGS assays, other mechanisms are involved in PD-L1 upregulation, especially in DLBCL. FISH assay may be more suitable than NGS assay for determination of PD-L1 alterations in cHL.
authors.affiliation: Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.|School of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Semir
authors.identifier: http://orcid.org/0000-0001-9743-7265
authors.initials: S
authors.lastname: Vranic
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Charlotte, North Carolina, United States of America.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Ghosh
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, United States of America.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Kimbrough
authors.affiliation: Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Nurija
authors.initials: N
authors.lastname: Bilalovic
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Bender
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Arguello
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, United States of America.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Veloso
authors.affiliation: Department of Hematology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
authors.forename: Aida
authors.initials: A
authors.lastname: Dizdarevic
authors.affiliation: Caris Life Sciences, Phoenix, Arizona, United States of America.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D056915:DNA Copy Number Variations; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008223:Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C507924:JAK2 protein, human; D053614:Janus Kinase 2