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Projekt Druckansicht

Auswirkungen von tumormetabolisch wirksamen Pharmaka auf die Effektorfunktionen von humanen CD8 T-Zellen

Fachliche Zuordnung Hämatologie, Onkologie
Förderung Förderung von 2014 bis 2019
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 190230491
 
Erstellungsjahr 2019

Zusammenfassung der Projektergebnisse

Our results clearly demonstrate that T cell effector functions can be preserved in the presence of metabolic inhibitors. Proliferation turned out to be more sensitive, however, even under administration of potent glycolytic inhibitors only a reduction was observed but not a complete blockade. The administration of diclofenac or lumiracoxib, blocking MCT1 and MCT4 and at the same time COX activity, thereby reducing the secretion of the immunosuppressive metabolite prostaglandine E2, turned out to be a promising strategy in the context of immunotherapeutic approaches, underlined by our first in vivo mouse experiments. With regard to glutamine metabolism, there seems to be a window for certain pathway inhibitors, whereas the application of glutamine analogues or pan-glutamine inhibitors most likely results in severe immunosuppression. Further evaluation is warranted to exclude adverse side effects. From the results obtained in this project we conclude, that the detailed analysis of the link between metabolism and CD8+ T cell function and the impact of anti-metabolic drugs reveal possible favourable combinations of anti-metabolic drugs and immunotherapeutic approaches (such as checkpoint inhibitors), which appear to strengthen the anti-tumor immune response and should be tested within clinical trials.

Projektbezogene Publikationen (Auswahl)

 
 

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