Personalizing checkpoint inhibitor therapy in melanoma patients by defining predictive factors and therapeutic approaches for the treatment of immune-mediated colitis

Checkpoint inhibitor therapies are more and more common in the treatment of cancer patients and response rates, even in patients with advanced cancers, are very promising. However, this therapeutic approach is limited by the fact that severe side effects are common, with immune-mediated colitis being the most frequent cause of treatment cessation and the initiation of immunosuppressive therapy. The identification of predictive markers for the onset of immune-mediated colitis will help to identify those patients who will benefit most from checkpoint inhibitor therapy while concomitantly minimizing side effects. This would greatly enhance the therapeutic success of the therapy, the quality of life of affected cancer patients while also providing strong socio-economic benefits. In collaboration with the Department of Dermatology, we aim at identifying predictive factors for the onset of immune-mediated colitis in patients with malignant melanoma. For this purpose, we will collect primary human peripheral mononuclear cells, serum, intestinal tissue samples and fecal samples from melanoma patients. Using those samples we will apply molecular approaches to study immune cell subsets, cytokine pattern, tissue markers and intestinal microbiota composition. The success of our approach represent crucial step in optimizing cancer therapy and establishing a personalized medicine. Our project will provide the direct translation from bedside to bench and vice versa and has the potential to change the paradigm of how we treat cancer patients.