Sektioglu, Ibrahim M. and Carretero, Rafael and Bender, Noemi and Bogdan, Christian and Garbi, Natalio and Umansky, Viktor and Umansky, Ludmila and Urban, Katharina and von Knebel-Doeberitz, Magnus and Somasundaram, Veena and Wink, David and Beckhove, Philipp and Haemmerling, Guenter J. (2016) Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection. ONCOIMMUNOLOGY, 5 (10): e1204506. ISSN 2162-402X,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; PANCREATIC-CANCER; ENDOTHELIAL-CELLS; EXPRESSION; INFILTRATION; MICE; INHIBITION; SYNTHASE; THERAPY; DIFFERENTIATION; Adoptive T-cell transfer; endothelial adhesion molecules; endothelial barrier; iNOS plus macrophage; NO; tumor therapy; T-cell infiltration |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2019 10:20 |
| Last Modified: | 18 Mar 2019 10:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2624 |
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