Deciphering the effects of ANG-2, VEGFR and PD-1 blockade in small cell lung cancer
Most of the SCLC patients do not benefit from first or second line immune checkpoint blockade as they either harbor primary resistance or acquire resistance during therapy. In order to overcome these resistances, our group combined Nivolumab treatment with blockade of Angiopoietin-2 (Ang-2) and the vascular endothelial growth factor (VEGF-A)/VEGFR2 signaling axis. This combination has been shown to improve the survival of the mice suffering from SCLC, compared to those treated with the monotherapy. My aim is to elucidate the effects of Ang-2 and VEGF-A on the tumor cells and cell types in the microenvironment. For this purpose, I will stimulate SCLC tumor cells, splenocytes of mice and peripheral blood mononuclear cells (PBMCs) of patients suffering from SCLC and investigate the expression of inhibitory immune checkpoint ligands, such as Programmed death ligand 1 (PD-L1), PD-L2 and Galectin-9 by fluorescence-activated cell sorting (FACS)-analysis.