Biomarkers for response to immune checkpoint inhibitors in metastatic melanoma

Melanoma is the most aggressive form of skin cancer. In the early stages of the disease, curative treatment can be provided by excision of the melanoma with or without lymph node dissection, sometimes followed by adjuvant therapy. For stage III melanoma with clinically detectable lymph nodes, neoadjuvant immunotherapy followed by surgery and sometimes adjuvant treatment is the standard of care. For patients with melanoma and distant metastases (stage IV), treatment with immune checkpoint inhibitors and/or mutation-targeted therapy is available. The latter treatments can lead to a durable response in a large proportion of patients. Despite the improvements in survival, more than 50% of patients with stage IV melanoma do not benefit sufficiently from treatment with immune checkpoint inhibitors. However, many patients suffer from one or more side effects. These side effects can be very serious in some cases. This dissertation aims to identify and investigate novel and emerging biomarkers that can be used to distinguish non-responders from responders. The relationship between response to immune checkpoint inhibitors and circulating tumor DNA, composition of the gut microbiome, gene expression within the melanoma, the occurrence of side effects and the biological uptake of a new tracer by means of PET scans were examined. In the future, the application of these methods may aid doctors to select the best treatment for the individual patient.