Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection

• Verfasst von: Sektioglu, Ibrahim Murathan [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Titel: Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection
• Verf.angabe: Ibrahim M. Sektioglu, Rafael Carretero, Noemi Bender, Christian Bogdan, Natalio Garbi, Viktor Umansky, Ludmila Umansky, Katharina Urban, Magnus von Knebel-Döberitz, Veena Somasundaram, David Wink, Philipp Beckhove and Günter J. Hämmerling
• E-Jahr: 2016
• Jahr: 27 Sep 2016
• Umfang: 13 S.
• Fussnoten: Gesehen am 19.02.2019
• Titel Quelle: Enthalten in: OncoImmunology
• Ort Quelle: Abingdon : Taylor & Franics, 2012
• Jahr Quelle: 2016
• Band/Heft Quelle: 5(2016,10) Artikel-Nummer e1204506, 13 Seiten
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2016.1204506
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adoptive T-cell transfer
• Sach-SW: endothelial adhesion molecules
• Sach-SW: endothelial barrier
• Sach-SW: iNOS+ macrophage
• Sach-SW: NO
• Sach-SW: T-cell infiltration
• Sach-SW: tumor therapy
• K10plus-PPN: 1587803992

Abstract

In tumor biology, nitric oxide (NO) is generally regarded as an immunosuppressive molecule that impedes T-cell functions and activation of endothelial cells. Contrasting with this view, we here describe a critical role for NO derived from inducible nitric oxide (iNOS)-expressing tumor macrophages in T-cell infiltration and tumor rejection as shown by iNOS gene deletion, inhibition of iNOS, or NO donors. Specifically, macrophage-derived NO was found to induce on tumor vessels adhesion molecules that were required for T-cell extravasation. Experiments with human endothelial cells revealed a bimodal dose-dependent effect of NO. High doses of NO donors were indeed suppressive but lower, more physiological concentrations, induced adhesion molecules in an NFkB-dependent pathway and preferentially activated transcription of genes involved in lymphocyte diapedesis. iNOS+ macrophages in tumors appear to generate precisely the amount of NO that promotes endothelial activation and T-cell infiltration. These results will be valuable for the development of strategies designed to overcome the paucity of T-cell infiltration into tumors that is a major obstacle in clinical cancer immunotherapy.