Coagulation signaling as a modulator for anti-tumor immunity
We showed that macrophages express the coagulation proteases FVII, FX and their receptors tissue factor and endothelial protein C receptor (EPCR). FX promotes tumor immune evasion. FXa inhibition led to increased abundance of antigen-presenting cells (APCs) and cytotoxic T-cells (CTL) in the tumor and synergized with checkpoint blockade. In contrast, our preliminary data implicate divergent effects of FVII and EPCR. In the second funding period, we will analyze effects of coagulation on the development of APCs and their ability for antigen presentation and CTL activation. Within the CRC, we will elucidate the clinical implications of coagulation protease expression by macrophages in malignancy.
(Bilder: Privat/Universitätsmedizin Mainz)