PhD defence B. Belderbos

Below is a brief summary of the dissertation: 

Pleural mesothelioma (PM) is a cancer of the lining of the lungs, primarily linked to asbestos exposure. Median survival after standard chemotherapy is poor (12–14 months), and although immunotherapy with checkpoint inhibitors (CI) has shown groundbreaking results in non-small cell lung cancer (NSCLC), the benefits in PM are limited—extending survival by only four months with dual CI therapy, often accompanied by significant toxicity.
For CI therapy to work effectively, a robust anti-tumour immune response is crucial. In PM, this response may be weakened due to a low mutation burden in cancer cells and poorly functioning dendritic cells, which normally act as key coordinators of the immune system.
This thesis explores whether dendritic cells (DCs) can be used therapeutically to improve survival in PM. The phase 3 DENIM study showed that maintenance DC therapy following chemotherapy did not prolong survival. However, DC therapy proved safe with minimal side effects. It also demonstrated that large-scale implementation of autologous cell therapy is feasible and that DC-induced immune activation correlated with progression-free survival.
To enhance the effectiveness of immunotherapy (DC and CI) in PM, a better understanding of resistance mechanisms is needed. This thesis investigates such mechanisms and explores combinations of DC therapy with CI or surgery in preclinical and early-phase clinical studies. Through these strategies, we aim to improve the immune response in a broader group of PM patients.