@misc{10481/107657,
year = {2016},
month = {8},
url = {https://hdl.handle.net/10481/107657},
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.},
organization = {Wilhelm Sander-Stiftung},
organization = {Deutsche Forschungsgemeinschaft SFB 704, SFB 643, SFB 1181},
organization = {University Hospital Erlangen (project A61)},
publisher = {Taylor & Francis},
keywords = {Cancer},
keywords = {Immunology},
keywords = {Macrophage},
keywords = {Nitric oxide},
title = {Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection},
doi = {10.1080/2162402X.2016.1204506},
author = {Sektioglu, Ibrahim M. and Carretero Coca, Rafael and Hämmerling, Günter J.},
}