UNIGE document Scientific Article
previous document  unige:2018  next document
add to browser collection
Title

Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expression

Authors
Kerl, Katrin
Shane, Ryan
Dupuis, Marc
Rook, Alain H.
French, Lars E.
Published in Blood. 2008, vol. 111, no. 9, p. 4780-7
Abstract Because of the low proliferative potential of tumor cells in patients with Sézary syndrome (SzS), their accumulation has been suggested to be due to defective regulation of apoptosis. We analyzed the sensitivity to soluble Fas-ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), 2 members of the TNF superfamily in peripheral blood leukocytes (PBL) from patients with SzS. Compared with healthy donors, CD4(+) cells from patients with SzS were completely resistant to FasL in 9 of 16 cases. Of these 9 FasL-resistant cases, 4 revealed a loss in Fas (CD95) expression, whereas the remaining 5 exhibited normal or enhanced Fas expression. In the latter 5 cases, the apoptosis inhibitor cFLIP was overexpressed in CD4(+)/CD26(-) tumor cells compared with CD4(+)/CD26(-) cells from Fas-expressing FasL-sensitive patients and healthy donors. Furthermore, resistance to TRAIL and tumor cell-restricted loss of TRAIL-receptor 2 were observed in 16 of 16 SzS PBLs. It is noteworthy that resistance to FasL could be overcome by the use of a hexameric FasL or upon exposure of SzS cells to interferon-alpha (IFN-alpha) or IFN-gamma, the latter by an increase of Fas expression. Our data on primary SzS lymphocytes reveal frequent resistance to apoptosis induced by FasL and TRAIL, which may contribute to their accumulation in patients with SzS and be relevant at a therapeutic level.
Keywords ApoptosisCASP8 and FADD-Like Apoptosis Regulating Protein/analysis/geneticsCase-Control StudiesFas Ligand Protein/pharmacologyGene Expression RegulationHumansReceptors, Death DomainReceptors, TNF-Related Apoptosis-Inducing Ligand/analysisSezary Syndrome/immunology/pathologySkin Neoplasms/immunology/pathologyT-Lymphocytes/pathologyTNF-Related Apoptosis-Inducing Ligand/pharmacology
Identifiers
PMID: 18314443
Full text
Structures
Research group Voies d'activation de l'immunité innée au niveau de la peau (156)
Citation
(ISO format)
CONTASSOT, Emmanuel et al. Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expression. In: Blood, 2008, vol. 111, n° 9, p. 4780-7. https://archive-ouverte.unige.ch/unige:2018

309 hits

0 download

Update

Deposited on : 2009-06-12

Export document
Format :
Citation style :