Unmet Needs Today and Treatment Goals of the Future: The Role of Immuno-Oncology Prof. Karim Vermaelen, UZ Gent on behalf of Sacha Rothschild MD PhD, University Hospital Basel
the 3 “E”s of tumor immunoediting immuno-editing: Elimination - Equilibrium - Escape Equilibrium Escape Elimination genetic instability vs selection pressure from the immune system selectie van immuno- resistente varianten toename van immuno- suppressieve signalen selectie van immuno- resistente varianten toename van immuno- suppressieve signalen tumor immunogenicity clinical detection / symptoms immune suppression clinical detection / symptoms immune suppression K.Vermaelen 2014
Immune Checkpoint inhibitors in combination therapy
Nivolumab + Erlotinib for EGFR mutant NSCLC
tumor-draining lymph node VEGF IL-6 IL-10 VEGF IL-6 IL-10 NO ROS Arginase NO ROS Arginase plasmacytoid DC tumor-associated macrophage myeloid suppressor cell tumor-associated macrophage myeloid suppressor cell regulatory T-cells IDO IL-10 IDO PDL1 IL-10 IDO PDL1 IL-10 TGF IL-10 TGF IL-10 TGF CTLA4 IL-10 TGF CTLA4 TGF VEGF IL-10 PGE2 TGF VEGF IL-10 PGE2 de antitumorale immuunrespons tumor escape mechanismen: netwerken van corruptie
KV paclitaxel induces tumoral infiltration by cytotoxic T-cells ➔ correlates with response Synergism between chemo- and immunotherapy Demaria et al, Clin Cancer Res 2001
KV Immunogenic cancer cell death chemotherapy IFN-g CD8+ cytotoxic T-cells