Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection

Sektioglu IM, Carretero R, Bender N, Bogdan C, Garbi N, Umansky V, Umansky L, Urban K, Von Knebel-Doeberitz M, Somasundaram V, Wink D, Beckhove P, Haemmerling GJ (2016)

Publication Type: Journal article

Publication year: 2016

Journal

OncoImmunology Taylor & Francis

Book Volume: 5

Pages Range: e1204506

Journal Issue: 10

DOI: 10.1080/2162402X.2016.1204506

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.

Authors with CRIS profile

Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) National Cancer Institute (NCI) US United States (USA) (US) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE)

How to cite

APA:

Sektioglu, I.M., Carretero, R., Bender, N., Bogdan, C., Garbi, N., Umansky, V.,... Haemmerling, G.J. (2016). Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection. OncoImmunology, 5(10), e1204506. https://doi.org/10.1080/2162402X.2016.1204506

MLA:

Sektioglu, Ibrahim M., et al. "Macrophage-derived nitric oxide initiates T-cell diapedesis and tumor rejection." OncoImmunology 5.10 (2016): e1204506.

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