6th Annual Symposium
Physics of Cancer
Leipzig, Germany
September 7-9, 2015
Invited Talk
Reinforcement of integrin-mediated T-lymphocyte adhesion by TNF
Christine Selhuber-Unkel1, Qian Li1, Dieter Adam2
1Biocompatible Nanomaterials, Institute for Materials Science, University of Kiel, Kiel, Germany
2Institute of Immunology, University of Kiel, Kiel, Germany
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Immunotherapy of cancer is currently the most promising strategy for an effective future treatment of tumor patients. As a prerequisite for the immunological response against tumor cells, lymphocytes need to be recruited from the bloodstream to the site of tumor formation. Here, the integrin-mediated T-lymphocyte adhesion to endothelial cells plays a key role. Whereas the outside-in signaling pathway of integrins in response to the proinflammatory cytokine tumor necrosis factor (TNF) has already been studied in detail, the inside-out signaling pathway of integrins in lymphocyte activation by TNF is rather unexplored. We employed single-cell force spectroscopy (SCFS) to elucidate the adhesion of T-lymphocyte (Jurkat E6-1) adhesion to biomimetic fibronectin layers. Fibronectin is naturally present on top of endothelial cell layers and is therefore a crucial player in mediating T-lymphocyte binding to endothelial cells. Our results show that stimulating integrins with TNF significantly increases the maximum adhesion force and detachment energy of Jurkat cells to fibronectin-coated surfaces. Analysis of individual rupture events further showed that TNF reinforces their binding strength, particularly at sub-second timescales. Hence, our results provide quantitative evidence for the significant impact of TNF-induced inside-out signaling in the T-lymphocyte adhesion machinery.
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