Abstracts (complete list) - Wissenschaft Online

Elke Pogge von Strandmmann, Boris Böll, Daniel Re, Andreas Engert, Venkateswara
Simhadri
Detection of HLA-B associated transcript 3 (BAT3) in sera
from Hodgkin Lymphoma patients and its release from
Hodgkin lymphoma cells
Major triggering NK cell receptors such as NKG2D and the Natural Cytotoxicity
Receptors Nkp30, 44 and 46 are critically involved in tumor cell recognition and
surveillance, since a decrease of the corresponding ligands on tumor cells correlates
with impaired NK cell-dependent killing and tumor progression. However, sustained
expression and the release of soluble ligands for the NKG2D receptor negatively
imprints the local and systemic immune response and correlates with a poor prognosis
for haematological and epithelial malignancies.
Hodgkin Lymphoma (HL) patients have impaired NK cell activity in the peripheral blood
and the level of NK anergy correlates with a bad prognosis. Since spleen derived NK
cells exhibit normal or increased activity, a serum-derived factor is probably involved in
NK cell inhibition. In order to asses the role of HLA-B-associated transcript 3 (BAT3), we
screened the sera of healthy donors and early and late stage HL patients using a BAT3
specific sandwich-ELISA. BAT3, recently characterized in our lab, is a tumor-released
ligand, that engages the triggering Natural Cytotoxicity Receptor NKp30. The BAT3
serum level was significantly elevated in HL patients in comparison to healthy donors
(p=0.0002). Interestingly, the early stage patients had a more pronounced increase
compared to the advanced stage patients (p=0.024). We next analyzed whether cellular
stress signals, such as HDAC inhibition and proteasomes inhibition could modulate the
expression/release of BAT3 from Hodkin lymphoma-derived cell lines. A panel of cell
lines were incubated with subtoxic concentrations of valproate and bortezomib and the
supernatants were collected for a BAT3-specific ELISA. A significant increase of BAT3 in
response to both substances was detected, that was irrespective of the IkB-a mutation
status of the cell lines. The analysis of released BAT3 using fractionation and Western
blotting revealed that different BAT3 isoforms were secreted, that may exhibit distinct
modulation of NK cell-activity.