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Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma

Hodgkin’s lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immunotherapies. To...

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Autores principales: Li, Wenchao, Blessin, Niclas C., Simon, Ronald, Kluth, Martina, Fischer, Kristine, Hube-Magg, Claudia, Makrypidi-Fraune, Georgia, Wellge, Björn, Mandelkow, Tim, Debatin, Nicolaus F., Pott, Laura, Höflmayer, Doris, Lennartz, Maximilian, Sauter, Guido, Izbicki, Jakob R., Minner, Sarah, Büscheck, Franziska, Uhlig, Ria, Dum, David, Krech, Till, Luebke, Andreas M., Wittmer, Corinna, Jacobsen, Frank, Burandt, Eike, Steurer, Stefan, Wilczak, Waldemar, Hinsch, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280445/
https://www.ncbi.nlm.nih.gov/pubmed/30514251
http://dx.doi.org/10.1186/s12885-018-5111-1
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author Li, Wenchao
Blessin, Niclas C.
Simon, Ronald
Kluth, Martina
Fischer, Kristine
Hube-Magg, Claudia
Makrypidi-Fraune, Georgia
Wellge, Björn
Mandelkow, Tim
Debatin, Nicolaus F.
Pott, Laura
Höflmayer, Doris
Lennartz, Maximilian
Sauter, Guido
Izbicki, Jakob R.
Minner, Sarah
Büscheck, Franziska
Uhlig, Ria
Dum, David
Krech, Till
Luebke, Andreas M.
Wittmer, Corinna
Jacobsen, Frank
Burandt, Eike
Steurer, Stefan
Wilczak, Waldemar
Hinsch, Andrea
author_facet Li, Wenchao
Blessin, Niclas C.
Simon, Ronald
Kluth, Martina
Fischer, Kristine
Hube-Magg, Claudia
Makrypidi-Fraune, Georgia
Wellge, Björn
Mandelkow, Tim
Debatin, Nicolaus F.
Pott, Laura
Höflmayer, Doris
Lennartz, Maximilian
Sauter, Guido
Izbicki, Jakob R.
Minner, Sarah
Büscheck, Franziska
Uhlig, Ria
Dum, David
Krech, Till
Luebke, Andreas M.
Wittmer, Corinna
Jacobsen, Frank
Burandt, Eike
Steurer, Stefan
Wilczak, Waldemar
Hinsch, Andrea
author_sort Li, Wenchao
collection PubMed
description Hodgkin’s lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immunotherapies. To study patterns of TIGIT expression in the T cell background surrounding malignant cells including Hodgkin cells, Reed-Sternberg cells and histiocytic cells, a microenvironment (ME) tissue microarray (TMA) was constructed from tissue punches measuring 2 mm in diameter obtained from formalin-fixed tissue samples of Hodgkin’s lymphoma lymph nodes (n = 40) and normal human tonsil (n = 2). The ME-TMA was stained by brightfield and fluorescence multiplex immunohistochemistry (IHC) to evaluate expression levels of TIGIT and PD-1 as well as standard lymphocyte markers (CD3, CD8, CD4, FOXP3) in the lymphocytic background. All analyzed cases of HL contained 9–99% (median: 86%) of TIGIT(+) lymphoid cells. In general, TIGIT localized to the same cells as PD-1. Strikingly, expression levels of TIGIT and PD-1 were highly variable among the analyzed samples. Highest levels of TIGIT and PD-1 were found in one sample of nodular lymphocytic-predominant HL (NLPHL). In conclusion, TIGIT expression is highly variable between patients with Hodgkin’s lymphoma. Our results encourage further studies evaluating the role of TIGIT as a target for immunotherapies in Hodgkin’s lymphoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5111-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-62804452018-12-10 Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma Li, Wenchao Blessin, Niclas C. Simon, Ronald Kluth, Martina Fischer, Kristine Hube-Magg, Claudia Makrypidi-Fraune, Georgia Wellge, Björn Mandelkow, Tim Debatin, Nicolaus F. Pott, Laura Höflmayer, Doris Lennartz, Maximilian Sauter, Guido Izbicki, Jakob R. Minner, Sarah Büscheck, Franziska Uhlig, Ria Dum, David Krech, Till Luebke, Andreas M. Wittmer, Corinna Jacobsen, Frank Burandt, Eike Steurer, Stefan Wilczak, Waldemar Hinsch, Andrea BMC Cancer Research Article Hodgkin’s lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immunotherapies. To study patterns of TIGIT expression in the T cell background surrounding malignant cells including Hodgkin cells, Reed-Sternberg cells and histiocytic cells, a microenvironment (ME) tissue microarray (TMA) was constructed from tissue punches measuring 2 mm in diameter obtained from formalin-fixed tissue samples of Hodgkin’s lymphoma lymph nodes (n = 40) and normal human tonsil (n = 2). The ME-TMA was stained by brightfield and fluorescence multiplex immunohistochemistry (IHC) to evaluate expression levels of TIGIT and PD-1 as well as standard lymphocyte markers (CD3, CD8, CD4, FOXP3) in the lymphocytic background. All analyzed cases of HL contained 9–99% (median: 86%) of TIGIT(+) lymphoid cells. In general, TIGIT localized to the same cells as PD-1. Strikingly, expression levels of TIGIT and PD-1 were highly variable among the analyzed samples. Highest levels of TIGIT and PD-1 were found in one sample of nodular lymphocytic-predominant HL (NLPHL). In conclusion, TIGIT expression is highly variable between patients with Hodgkin’s lymphoma. Our results encourage further studies evaluating the role of TIGIT as a target for immunotherapies in Hodgkin’s lymphoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-5111-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-04 /pmc/articles/PMC6280445/ /pubmed/30514251 http://dx.doi.org/10.1186/s12885-018-5111-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Li, Wenchao
Blessin, Niclas C.
Simon, Ronald
Kluth, Martina
Fischer, Kristine
Hube-Magg, Claudia
Makrypidi-Fraune, Georgia
Wellge, Björn
Mandelkow, Tim
Debatin, Nicolaus F.
Pott, Laura
Höflmayer, Doris
Lennartz, Maximilian
Sauter, Guido
Izbicki, Jakob R.
Minner, Sarah
Büscheck, Franziska
Uhlig, Ria
Dum, David
Krech, Till
Luebke, Andreas M.
Wittmer, Corinna
Jacobsen, Frank
Burandt, Eike
Steurer, Stefan
Wilczak, Waldemar
Hinsch, Andrea
Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
title Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
title_full Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
title_fullStr Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
title_full_unstemmed Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
title_short Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
title_sort expression of the immune checkpoint receptor tigit in hodgkin’s lymphoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280445/
https://www.ncbi.nlm.nih.gov/pubmed/30514251
http://dx.doi.org/10.1186/s12885-018-5111-1
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