P8 Targeting of monocytes and macrophages by myxobacterial compounds as anti-cancer strategy

Monocytes and macrophages (including M1 and M2 subtypes) constitute functional components of tumors, creating a tumor-promoting environment and thus represent interesting targets for antitumor therapy. Preliminary work focused on the modulation of human monocytes and macrophage subsets by archazolid and pretubulysin, and revealed remarkable biological properties to intervene with inflammation-triggered cancer.
The project will now investigate how archazolid (I) targets eicosanoid release, (II) differentially modulates cytokine secretion in monocytes and macrophages, and (III) regulates monocyte-macrophage differentiation, macrophage activation, and induction of differentiation towards dendritic cells, involving V-ATPase. For pretubulysin, the mode of action underlying the inhibition of TNFα release will be revealed. A lipidomic approach in monocytes/macrophages shall elucidate alterations induced by soraphen A which might be responsible for its antitumoral effects.

Principal investigator:

• Oliver Werz, Friedrich-Schiller-Universität Jena

DFG-funded scientists: 

• Saskia Lindner, PhD student

Associated scientists: 

• Dr. Andreas Koeberle
• Lea Thomas, PhD student