High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas

Maria Raffaella Zocchi, Silvia Catellani, Paolo Canevali, Sara Tavella, Anna Garuti, Barbara Villaggio, Annalisa Zunino, Marco Gobbi, Giulio Fraternali-Orcioni, Annalisa Kunkl, Jean Louis Ravetti, Silvia Boero, Alessandra Musso, Alessandro Poggi

Research output: Contribution to journalArticlepeer-review

Abstract

Herein we describe that in classic Hodgkin lymphomas (cHL, n = 25) the lymph node (LN) stroma displayed in situ high levels of transcription and expression of the disulfide-isomerase ERp5 and of the disintegrin- metalloproteinase ADAM10, able to shed the ligands for NKG2D (NKG2D-L) from the cell membrane. These enzymes were detected both in LN mesenchymal stromal cells (MSCs) and in Reed-Sternberg (RS) cells; in addition, MIC-A and ULBP3 were present in culture supernatants of LN MSCs or RS cells. NKG2D-L-negative RS cells could not be killed by CD8 +αβT or γδT cells; tumor cell killing was partially restored by treating RS cells with valproic acid, which enhanced NKG2D-L surface expression. Upon coculture with LN MSCs, CD8 +αβT and γδT cells strongly reduced their cytolytic activity against NKG2D-L + targets; this seems to be the result of TGF-β, present at the tumor site, produced in vitro by LN MSCs and able to down-regulate the expression of NKG2D on T lymphocytes. In addition, CD8 +αβT and γδT cells from the lymph nodes of cHL patients, cocultured in vitro with LN MSCs, underwent TGF-β-mediated down regulation of NKG2D. Thus, in cHL the tumor microenvironment is prone to inhibit the development of an efficient antitumor response.

Original languageEnglish
Pages (from-to)1479-1489
Number of pages11
JournalBlood
Volume119
Issue number6
DOIs
Publication statusPublished - Feb 9 2012

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of 'High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas'. Together they form a unique fingerprint.

Cite this