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000130541 0247_ $$2doi$$a10.1080/2162402X.2016.1204506
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000130541 0247_ $$2ISSN$$a2162-402X
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000130541 1001_ $$0P:(DE-HGF)0$$aSektioglu, Ibrahim M$$b0$$eFirst author
000130541 245__ $$aMacrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection.
000130541 260__ $$aAustin, Tex.$$bLandes Bioscience$$c2016
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000130541 520__ $$aIn tumor biology, nitric oxide (NO) is generally regarded as an immunosuppressive molecule that impedes T-cell functions and activation of endothelial cells. Contrasting with this view, we here describe a critical role for NO derived from inducible nitric oxide (iNOS)-expressing tumor macrophages in T-cell infiltration and tumor rejection as shown by iNOS gene deletion, inhibition of iNOS, or NO donors. Specifically, macrophage-derived NO was found to induce on tumor vessels adhesion molecules that were required for T-cell extravasation. Experiments with human endothelial cells revealed a bimodal dose-dependent effect of NO. High doses of NO donors were indeed suppressive but lower, more physiological concentrations, induced adhesion molecules in an NFkB-dependent pathway and preferentially activated transcription of genes involved in lymphocyte diapedesis. iNOS(+) macrophages in tumors appear to generate precisely the amount of NO that promotes endothelial activation and T-cell infiltration. These results will be valuable for the development of strategies designed to overcome the paucity of T-cell infiltration into tumors that is a major obstacle in clinical cancer immunotherapy.
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000130541 7001_ $$0P:(DE-He78)86723b26e79aa190a6c7294651a80986$$aCarretero, Rafael$$b1$$udkfz
000130541 7001_ $$0P:(DE-He78)540833b33724d8def638cce2f0b4e187$$aBender, Noemi$$b2$$udkfz
000130541 7001_ $$aBogdan, Christian$$b3
000130541 7001_ $$aGarbi, Natalio$$b4
000130541 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, Viktor$$b5$$udkfz
000130541 7001_ $$0P:(DE-He78)d5882ffec9d5dea0104c7d33165e4a45$$aUmansky, Ludmila$$b6$$udkfz
000130541 7001_ $$0P:(DE-He78)9cafc6ecff7e1f32c9d4644c841740cb$$aUrban, Katharina$$b7$$udkfz
000130541 7001_ $$0P:(DE-He78)21aa945a14aa0e9a9ce522c6f43e73e7$$aKnebel Döberitz, Christina$$b8$$udkfz
000130541 7001_ $$aSomasundaram, Veena$$b9
000130541 7001_ $$aWink, David$$b10
000130541 7001_ $$0P:(DE-He78)1732377f6242a18280bc6aaa196988d1$$aBeckhove, Philipp$$b11$$udkfz
000130541 7001_ $$0P:(DE-He78)5f9901fc60b769b523d0dd8e79b3fe08$$aHämmerling, Günter$$b12$$eLast author$$udkfz
000130541 773__ $$0PERI:(DE-600)2645309-5$$a10.1080/2162402X.2016.1204506$$gVol. 5, no. 10, p. e1204506 -$$n10$$pe1204506 -$$tOncoImmunology$$v5$$x2162-402X$$y2016
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