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.

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Presentation transcript:

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