The long-term outcome of melanoma patients who respond to immune checkpoint inhibition (ICI) therapy is highly favorable. However, half of the patients still fail to respond to ICI therapy and only a few predictive biomarkers are available to predict response.
This project aims to demonstrate that high intratumoral heterogeneity leads to an impaired ICI therapy outcome in melanoma. As potential factors influencing this intratumoral heterogeneity, the expression of Human Endogenous RetroVirus K (HERV-K) and its potential association with the site of metastasis (liver versus other organs) will be investigated.  
Tumor tissue samples from ICI responders (CR/PR) and non-responders (PD) will be analyzed by broad low-resolution and focussed high-resolution spatial transcriptomics and antibody-based spatial proteomics. These molecular analyses will be performed on pre-therapeutic FFPE tumor tissue samples from patients who have received PD-1-based ICI for non-resectable melanoma within the multicenter translational study TRIM (CA209-578; NCT05750511) of ADO/DeCOG.