Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection
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...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 Sep 2016
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| In: |
OncoImmunology
Year: 2016, Volume: 5, Issue: 10 |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2016.1204506 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1080/2162402X.2016.1204506 Verlag, Volltext: https://doi.org/10.1080/2162402X.2016.1204506 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 19.02.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2016.1204506 |