Universität zu Köln

Brinkmann, Kerstin, Hombach, Andreas, Seeger, Jens Michael, Wagner-Stippich, Diana, Klubertz, Daniela, Kroenke, Martin, Abken, Hinrich and Kashkar, Hamid (2014). Second mitochondria-derived activator of caspase (SMAC) mimetic potentiates tumor susceptibility toward natural killer cell-mediated killing. Leuk. Lymphoma, 55 (3). S. 645 - 652. ABINGDON: TAYLOR & FRANCIS LTD. ISSN 1029-2403

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Abstract

Resistance to apoptosis is a hallmark of cancer, and represents an important mechanism of how tumor cells resist immune cell destruction. Mitochondria are the central regulators of the apoptotic machinery by releasing pro-apoptotic factors including cytochrome c and second mitochondria-derived activator of caspase (SMAC) upon mitochondrial outer membrane permeabilization (MOMP). Small molecules activating MOMP such as BH3 mimetics or antagonizers of the inhibitor of apoptosis proteins (IAPs) such as SMAC mimetics have recently engendered new optimism for a more individualized and effective cancer therapy. Here we show that a SMAC mimetic potentiates cancer cell killing by natural killer (NK) cells through reactivation of tumor cell apoptosis. Specifically, the SMAC mimetic enhances the susceptibility of tumor cells toward NK cell-mediated effector mechanisms involving death receptors and cytolytic granules containing perforin and granzymes by relieving caspase activity. Our data highlight for the first time the specific use of SMAC mimetics for boosting immune cell-mediated immunotherapy, representing a novel and promising approach in the treatment of cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brinkmann, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger, Jens Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner-Stippich, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Klubertz, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-444991
DOI:	10.3109/10428194.2013.807925
Journal or Publication Title:	Leuk. Lymphoma
Volume:	55
Number:	3
Page Range:	S. 645 - 652
Date:	2014
Publisher:	TAYLOR & FRANCIS LTD
Place of Publication:	ABINGDON
ISSN:	1029-2403
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language X-LINKED INHIBITOR; NF-KAPPA-B; GRANZYME-B; CYTOCHROME-C; APOPTOSIS PROTEINS; XIAP; HODGKIN; CANCER; EXPRESSION; REQUIRES Multiple languages Oncology; Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44499