Published in:
Open Access
01-12-2018 | Research article
Expression of the immune checkpoint receptor TIGIT in Hodgkin’s lymphoma
Authors:
Wenchao Li, Niclas C. Blessin, Ronald Simon, Martina Kluth, Kristine Fischer, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Björn Wellge, Tim Mandelkow, Nicolaus F. Debatin, Laura Pott, Doris Höflmayer, Maximilian Lennartz, Guido Sauter, Jakob R. Izbicki, Sarah Minner, Franziska Büscheck, Ria Uhlig, David Dum, Till Krech, Andreas M. Luebke, Corinna Wittmer, Frank Jacobsen, Eike Burandt, Stefan Steurer, Waldemar Wilczak, Andrea Hinsch
Published in:
BMC Cancer
|
Issue 1/2018
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Abstract
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.