TY  - JOUR
AU  - Sektioglu, Ibrahim M
AU  - Carretero, Rafael
AU  - Bender, Noemi
AU  - Bogdan, Christian
AU  - Garbi, Natalio
AU  - Umansky, Viktor
AU  - Umansky, Ludmila
AU  - Urban, Katharina
AU  - Knebel Döberitz, Christina
AU  - Somasundaram, Veena
AU  - Wink, David
AU  - Beckhove, Philipp
AU  - Hämmerling, Günter
TI  - Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection.
JO  - OncoImmunology
VL  - 5
IS  - 10
SN  - 2162-402X
CY  - Austin, Tex.
PB  - Landes Bioscience
M1  - DKFZ-2017-05620
SP  - e1204506 -
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:27853636
C2  - pmc:PMC5087300
DO  - DOI:10.1080/2162402X.2016.1204506
UR  - https://inrepo02.dkfz.de/record/130541
ER  -