Cargando…

PD-L1 Status in Refractory Lymphomas

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 treat...

Descripción completa

Detalles Bibliográficos
Autores principales: Vranic, Semir, Ghosh, Nilanjan, Kimbrough, Jeffery, Bilalovic, Nurija, Bender, Ryan, Arguello, David, Veloso, Yvonne, Dizdarevic, Aida, Gatalica, Zoran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115714/
https://www.ncbi.nlm.nih.gov/pubmed/27861596
http://dx.doi.org/10.1371/journal.pone.0166266
_version_ 1782468557671497728
author Vranic, Semir
Ghosh, Nilanjan
Kimbrough, Jeffery
Bilalovic, Nurija
Bender, Ryan
Arguello, David
Veloso, Yvonne
Dizdarevic, Aida
Gatalica, Zoran
author_facet Vranic, Semir
Ghosh, Nilanjan
Kimbrough, Jeffery
Bilalovic, Nurija
Bender, Ryan
Arguello, David
Veloso, Yvonne
Dizdarevic, Aida
Gatalica, Zoran
author_sort Vranic, Semir
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5115714
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-51157142016-12-08 PD-L1 Status in Refractory Lymphomas Vranic, Semir Ghosh, Nilanjan Kimbrough, Jeffery Bilalovic, Nurija Bender, Ryan Arguello, David Veloso, Yvonne Dizdarevic, Aida Gatalica, Zoran PLoS One Research Article 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. Public Library of Science 2016-11-18 /pmc/articles/PMC5115714/ /pubmed/27861596 http://dx.doi.org/10.1371/journal.pone.0166266 Text en © 2016 Vranic et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vranic, Semir
Ghosh, Nilanjan
Kimbrough, Jeffery
Bilalovic, Nurija
Bender, Ryan
Arguello, David
Veloso, Yvonne
Dizdarevic, Aida
Gatalica, Zoran
PD-L1 Status in Refractory Lymphomas
title PD-L1 Status in Refractory Lymphomas
title_full PD-L1 Status in Refractory Lymphomas
title_fullStr PD-L1 Status in Refractory Lymphomas
title_full_unstemmed PD-L1 Status in Refractory Lymphomas
title_short PD-L1 Status in Refractory Lymphomas
title_sort pd-l1 status in refractory lymphomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115714/
https://www.ncbi.nlm.nih.gov/pubmed/27861596
http://dx.doi.org/10.1371/journal.pone.0166266
work_keys_str_mv AT vranicsemir pdl1statusinrefractorylymphomas
AT ghoshnilanjan pdl1statusinrefractorylymphomas
AT kimbroughjeffery pdl1statusinrefractorylymphomas
AT bilalovicnurija pdl1statusinrefractorylymphomas
AT benderryan pdl1statusinrefractorylymphomas
AT arguellodavid pdl1statusinrefractorylymphomas
AT velosoyvonne pdl1statusinrefractorylymphomas
AT dizdarevicaida pdl1statusinrefractorylymphomas
AT gatalicazoran pdl1statusinrefractorylymphomas