Direct and natural killer cell-mediated antitumor effects of CB1 receptor antagonist rimonabant in human glioblastoma.

Abstract

Event Abstract Back to Event Direct and natural killer cell-mediated antitumor effects of CB1 receptor antagonist rimonabant in human glioblastoma. Elena Ciaglia1, 2*, Simona Pisanti1, 2, Paola Picardi2, Chiara Laezza3, Giovanni Torelli4, Patrizia Gazzerro2 and Maurizio Bifulco1, 2 1 University of Salerno, Medicine and Surgery, Italy 2 University of Salerno, Pharmacy, Italy 3 IEOS CNR, Institute of Endocrinology and Experimental Oncology, Italy 4 "G.Rummo" Hospital, Neurosurgery, Italy The failure of conventional cancer therapy renders glioblastoma (GBM) an attractive target for novel combined chemoimmunotherapeutic strategies. In the last years the pharmacological tuning of (endo)cannabinoid system has constituted a promising tool for the management of GBM patients. In this study we investigated the therapeutic exploitation of CB1 inactivation with regard to direct and NK cell-mediated effects against GBM. We show for the first time that Rimonabant treatment inhibited growth and viability of a panel of human glioma cell lines in both monolayer culture and 3D Minitumour spheroid models by decreasing the expression levels of Bcl-2, Bcl-XL and Survivin anti-apoptotic factors and concomitantly by inducing tumor necrosis factor (TNF)-related apoptosis-inducing ligand death receptor 4 (DR4) and DR5. Interestingly Rimonabant lead also to functional expression of MHC class I-related chain A and B (MICA/B) on surface of malignant p53mut U251MG and T98G glioma cell lines but not on normal human astrocyte (NHA). This make GBM cells potent targets for natural killer (NK) cell mediated recognition through a NKG2D restricted mechanism, thus stimulating cytotoxicity and IFN-Ƴ production of cocultured NK cells. This last effect relies on the inhibition of STAT3 signaling, whose constitutive activity has been previously seen to promote escape to NKG2D-mediated immune-surveillance. Our study suggests that, in addition to the direct cytotoxic effect, Rimonabant also can make GBM immunovisible priming it for NK cell antitumor reactivity. Taking into account that the brain tumor microenvironment is more commonly associated to CD56-positive NK cells, GBM patients may benefit from Rimonabant treatment. Acknowledgements This study was supported by Associazione Italiana Ricerca sul Cancro (AIRC; Investigator Grant IG 13312 to M.B.) E.Ciaglia was supported by a fellowship from FIRC -Fondazione Italiana Ricerca sul Cancro. Keywords: CB1 receptor, NK cell, Glioblastoma, ULBP, STAT3 Transcription Factor Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Ciaglia E, Pisanti S, Picardi P, Laezza C, Torelli G, Gazzerro P and Bifulco M (2013). Direct and natural killer cell-mediated antitumor effects of CB1 receptor antagonist rimonabant in human glioblastoma.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00048 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Elena Ciaglia, University of Salerno, Medicine and Surgery, Baronissi (Salerno), 84081, Italy, eciaglia@unisa.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elena Ciaglia Simona Pisanti Paola Picardi Chiara Laezza Giovanni Torelli Patrizia Gazzerro Maurizio Bifulco Google Elena Ciaglia Simona Pisanti Paola Picardi Chiara Laezza Giovanni Torelli Patrizia Gazzerro Maurizio Bifulco Google Scholar Elena Ciaglia Simona Pisanti Paola Picardi Chiara Laezza Giovanni Torelli Patrizia Gazzerro Maurizio Bifulco PubMed Elena Ciaglia Simona Pisanti Paola Picardi Chiara Laezza Giovanni Torelli Patrizia Gazzerro Maurizio Bifulco Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.