Cutane maligne melanomen: de rol van autofagie in chemotherapie-gemedieerde immunogene apoptose.

The scope of this project is to find new therapeutic avenues to circumvent the chemotherapy-resistance of metastatic melanoma skin cancer. In particular, the project addresses the role of autophagy, a major catabolic pathway for proteins and organelle degradation, in the immunological impact of metastatic melanoma cells, dying in response to clinically used chemotherapeutics. We will scrutinize the surface proteome and secretome of melanoma cells dying in response to clinically used chemotherapeutics to identify new danger-associated molecular patterns (DAMPs) and unravel their role in boosting innate immunity responses. We will evaluate whether these DAMPs can be found circulating in the blood of melanoma patients after chemotherapy. We will address molecular mechanisms of immunogenic melanoma cell death induced by these chemotherapeutics and use suitable tumor vaccination models to examine the role of autophagy suppression in adaptive immunity. Exploring the interplay between dying cancer cells and immune system may provide new and efficient therapeutic opportunities to fight metastatic melanoma, which combine cancer killing and antitumor immunity in one paradigm.

Trefwoorden:Proteomics, Anti-tumor immunity, Cell death, Chemotherapy, DAMPs, Melanoma, Autophagy