PD-L1 Status in Refractory Lymphomas

• Published in: PloS one 2016-11, Vol.11 (11), p.e0166266-e0166266
• Main Authors: Vranic, Semir, Ghosh, Nilanjan, Kimbrough, Jeffery, Bilalovic, Nurija, Bender, Ryan, Arguello, David, Veloso, Yvonne, Dizdarevic, Aida, Gatalica, Zoran
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amplification; Analysis; Antibodies; Assaying; Automation; B-cell lymphoma; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor; Breast cancer; Cancer; Care and treatment; Chronic lymphocytic leukemia; Cloning; Copy number; DNA Copy Number Variations; Drug Resistance, Neoplasm; Female; Fluorescence; Gene amplification; Gene Expression; High-Throughput Nucleotide Sequencing; Hodgkin's disease; Hodgkin's lymphoma; Humans; Immunoglobulins; Immunohistochemistry; Immunotherapy; In Situ Hybridization, Fluorescence; Janus kinase 2; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; Laboratories; Life sciences; Ligands; Lung cancer; Lymphocytes B; Lymphocytes T; Lymphoma; Lymphoma - diagnosis; Lymphoma - drug therapy; Lymphoma - genetics; Lymphoma - metabolism; Male; Medical research; Medicine and Health Sciences; Medicine, Experimental; Middle Aged; Non-Hodgkin's lymphomas; Patients; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Protein expression; Proteins; Research and Analysis Methods; Solid tumors; T cells; Tumors; Viral antibodies; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166266

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.