SP3 - MelAutim

Profiling of melanoma and autoimmunity patients

The aim of the subproject is to generate comparative data on markers predisposing or preventing autoimmunity in cancer patients. The project will focus on melanoma patients with and without autoimmune side effects under immunotherapy and compare those with patients who exhibit autoimmune disease. Predictive factors for developing autoimmune disease are known but so far these have not been characterized for autoimmunity induced by checkpoint inhibitors. For cohorts of patients with autoimmune disease and melanoma, we will assess a multi-level set of immune parameters, including HLA genotyping, leukocyte composition, and plasma levels of chemokines, cytokines and other soluble factors. The subproject is divided in two phases. In the first three years we will collect and process data from an exploration patient cohort, and use data analysis techniques, as well as network and enrichment analysis to identify potential markers for the emergence or exacerbation of autoimmunity in melanoma patients under immunotherapy. Our results will be cross-compared with the in silico signatures obtained from the computational models developed in SP4 and SP5, as well as with the experimentally derived markers from SP1 and SP2. In the last two years of the project, we will collect, process, and quantify samples from a validation patient cohort, which will be used to assess the significance of the predicted signatures and markers. Resulting phenotypic and molecular markers will aid in the future to perform a risk assessment of patients before initiation of therapy and to adapt therapy of autoimmunity to the specific inflammatory mechanisms in this setting.