Universität zu Köln

Klein, Jan M., Henke, Alexander, Sauer, Maike, Bessler, Martina, Reiners, Katrin S., Engert, Andreas, Hansen, Hinrich P. and von Strandmann, Elke Pogge (2013). The Histone Deacetylase Inhibitor LBH589 (Panobinostat) Modulates the Crosstalk of Lymphocytes with Hodgkin Lymphoma Cell Lines. PLoS One, 8 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Epigenetic changes have been implicated in the malignant phenotype of Hodgkin Reed Sternberg (HRS) cells in Hodgkin lymphoma (HL), where HRS survival and proliferation depends on the microenvironment. The histone-deacetylase (HDAC) inhibitor LBH589 (panobinostat) showed clinical efficacy but its impact on the HRS microenvironment is unclear. Hence, we analysed the effects of LBH589 on lymphocytes and also potential combination therapies. In lymphocyte-target cell killing assays, LBH589-treatment triggered an enhanced lymphocyte-dependent lysis of HL cells despite of mild lymphocytopenic effects. In co-culture experiments of lymphocytes with HL cells, LBH589 suppressed the IFNgamma-release but increased the TNFalpha secretion. Recombinant TNFalpha boosted the lymphocyte-dependent lysis of HL target cells. In HL cell lines, LBH589 induced cell death, autophagy, and an increase of MICA/B that are ligands to natural killer cell receptors. The combination of LBH589 with Brentuximab Vedotin was inefficient due to down-regulation of CD30 as a target. Combination with gemcitabine revealed highly significant effects, suggesting a potential combination for future therapy. Based on these data we suggest that LBH589 favourably modulates the cytokine network and lymphocyte activity in the HL microenvironment.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, Jan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Henke, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Sauer, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Bessler, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiners, Katrin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Engert, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Hinrich P. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Strandmann, Elke Pogge UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-471870
DOI:	10.1371/journal.pone.0079502
Journal or Publication Title:	PLoS One
Volume:	8
Number:	11
Date:	2013
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REED-STERNBERG CELLS; IN-VITRO; GEMCITABINE; EXPRESSION; INCREASES; THERAPY; CANCER; DEATH; CD30 Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47187