BMC Cancer (Dec 2018)

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

  • 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

DOI
https://doi.org/10.1186/s12885-018-5111-1
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 8

Abstract

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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.

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